TY - JOUR. T1 - Blockade of the Serotonin 5-HT 2A Receptor Suppresses Cue-Evoked Reinstatement of Cocaine-Seeking Behavior in a Rat Self-Administration Model. AU - Dhonnchadha, B. Á Nic. AU - Fox, R. G.. AU - Stutz, S. J.. AU - Rice, K. C.. AU - Cunningham, Kathryn. PY - 2009/4. Y1 - 2009/4. N2 - The serotonin 5-HT 2A receptor (5-HT 2AR) may play a role in reinstatement of drug-seeking. This study investigated the ability of a selective 5-HT 2AR antagonist to suppress reinstatement evoked by exposure to cues conditioned to cocaine self-administration. Cocaine self-administration (0.75 mg/kg/0.1 mL/6 s infusion; FR 4) was trained in naïve, free-fed rats to allow interpretation of results independent from changes related to food deprivation stress. Pretreatment with the selective 5-HT 2AR antagonist M100907 (volinanserin) failed to reduce rates of operant responding for cocaine infusions. On the other hand, M100907 (0.001-0.8 mg/kg ip) significantly suppressed the cue-induced reinstatement of ...
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Using an intravenous drug self-administration model in squirrel monkeys, we found that 2-AG, like THC, cocaine, and other abused drugs, was an effective reinforcer of drug-taking behavior. 2-AG was self-administered by monkeys that had a cannabinoid self-administration history (anandamide monkeys), as well as by monkeys with no history of cannabinoid self-administration (nicotine monkeys). The fact that 2-AG maintained drug-taking behavior in monkeys without a cannabinoid self-administration history suggests that the reinforcing effects of 2-AG were not dependent on prior self-administration of a particular class of drugs. Rates of responding maintained by 2-AG injections were comparable to those maintained under the same conditions by THC, anandamide, methanandamide (a metabolism-resistant analog of anandamide), or cocaine injections in our previous studies (Tanda et al., 2000; Justinova et al., 2003, 2005, 2008).. Although the rates of responding maintained by 2-AG injections were comparable ...
Cocaine self-administration studies in animals such as mice and rats are helping to clarify the mechanisms and controls of cocaine reward and abuse. Self-administration studies are commonly done in rats using a catheter which is placed into a vein or directly into the brain. Researchers who choose to study the genetics of addiction and self-administration find mice are considerably more useful than rats. This is because their entire genome is sequenced and because we have the ability to mutate or knock out specific genes and then determine the changes in the mice without functional use of these genes. The problem with trying to do cocaine experiments on mice is that due to their small size, it is difficult to properly place and maintain the catheters.. Animals normally respond more severely to repeated doses of cocaine, indicating they are sensitized to subsequent doses of the same concentration. Sensitization can be measured by an increase in repeated behaviors, referred to as stereotypies, ...
Cues present during cocaine self-administration become associated with the drug and if encountered during abstinence, increase the probability of relapse. However, despite much research on human relapse, including the use of animal behavioral models, the way in which relapse-inducing cues are interpreted by the user has remained elusive. Recent theories propose that, after long experience with self administration, drug taking shifts from goal-directed to a habit-like behavior, and therefore cues induce relapse automatically, thus bypassing information processing related to the consequences of relapse. But an alternative hypothesis is that relapse-inducing cues produce an expectation of the drugs consequences, triggering a goal-directed relapse. In animal behavioral experiments, a common procedure used to discriminate between habit and goal-directed responding is reward devaluation: if responding occurs despite devaluation, then the response is considered a habit, or automatic behavior; whereas, ...
Home-Cage Limited Access Drinking Paradigm. The following is a description of general procedures used for measuring voluntary EtOH self- administration in the home cage of mice under limited access conditions. Adult C57BL/6J mice are individually housed in pans with wood-chip bedding under a modified 12 hour light-dark cycle (lights on at 0300 hr). The mice are allowed to acclimate to this housing environment for a minimum of one week prior to the start of the study. Mice have free access to food (rodent lab chow) throughout the study. The animals are weighed once per week, at which time the pans are changed. Water bottles are changed as needed (usually twice per week). Mice are not food or water deprived throughout the study.. Using a modified sucrose-fading technique (Samson, 1986), mice are given daily access to EtOH for 2 hr in the home cage, beginning at 0.5 hr prior to the start of the dark cycle (1430 hr). Standard water bottles are removed and replaced with 15 ml bottles containing ...
Mice lacking Kalirin-7 (Kal7KO), a Rho GDP/GTP exchange factor, self-administer cocaine at a higher rate than wildtype mice, and show an exaggerated locomotor response to experimenter-administered cocaine. Kal7, which localizes to post-synaptic densities at glutamatergic synapses, interacts directly with the GluN2B subunit of the N-methyl-d-aspartate (NMDA; GluN) receptor. Consistent with these observations, Kal7 plays an essential role in NMDA receptor dependent long term potentiation and depression, and glutamatergic transmission plays a key role in the response to chronic cocaine. A number of genetic studies have implicated altered Kalirin expression in schizophrenia and other disorders such as Alzheimers Disease. A comparison of the effects of experimenter-administered cocaine on mice lacking all Kalirin isoforms to its effects on mice lacking only Kalirin-7 identified Kal7 as the key isoform whose deletion produces exaggerated locomotor responses to cocaine. Pretreatment of Kal7KO mice with a low
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As in previous studies using this and other progressive ratio schedules (Stafford et al., 1998; Wilcox et al., 2000), cocaine functioned as a positive reinforcer and responding increased with dose to an asymptote. (+)-CPCA also functioned as a positive reinforcer under the present progressive ratio schedule, confirming and extending previous self-administration results with this compound in monkeys maintained under a fixed ratio schedule (A. Kozikowski, personal communication). Responding maintained by (+)-CPCA increased with dose then decreased at the highest dose tested. Although only tested in one monkey, it is likely that cocaine-maintained responding would have decreased again had doses of 1.0 mg/kg/injection or higher been tested. In all but one monkey, cocaine was approximately 4-fold more potent than (+)-CPCA as a reinforcer. Maximum levels of responding were higher for cocaine than for (+)-CPCA. Doubling the TO after an injection from 30 to 60 min failed to increase cocaine or ...
Because Delta9-tetrahydrocannabinol (THC) has been a false negative in rat intravenous self-administration procedures, the evaluation of the abuse potential of candidate cannabinoid medications has proved difficult. One lab group has successfully trained self-administration of the aminoalkylindole WIN55,212-2 in rats; however, their results have not been independently replicated. The purpose of this study was to extend their model by using a within-subjects design, with the goal of establishing a robust method suitable for substitution testing of other cannabinoids.
Food maintained responding in mice. Mice were placed in the operant chambers for up to 3 hr/d, 5-7 d per week. Mice were first acclimated to the food that was subsequently used to reinforce operant responding. Mice were deprived of food for 20 hr, which resulted in a mean reduction in body weight of ∼5%. Mice were then placed in test chambers for 2 hr with the fan and house light activated and with a small cup containing 5 ml of vanilla-flavored Ensure (a nutritional supplement, hereafter referred to as "liquid food"; Abbott Laboratories, Columbus, OH). After the acclimation session, mice were given 3 gm each of mouse chow in their home cage. This procedure was repeated until a minimum of 1.5 ml of liquid food was consumed during a 2 hr acclimation session (typically within one or two sessions). Thereafter, mouse chow was available ad libitumin the home cage, and the small cup was removed from the test chamber.. During subsequent 2 hr sessions, liquid food was available under a fixed ratio ...
He said that if he were pastor of a church, in addition to a number of Ash Wednesday services, he would leave the ashes available for self-administration. There was no mention of documental permission for that practice, but the justification he gave was that the ashes are a sacramental (not a sacrament) and like holy water could be self-administered even by a layperson ...
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Fig. 1 Prior alcohol use enhances persistence, motivation, and compulsivity for cocaine self-administration.. (A) Drug treatment paradigm to study alcohol and cocaine coadministration. Access to voluntary alcohol (10% alcohol, 2 hours per day) and voluntary cocaine (self-administration, 0.8 mg/kg per injection) was restricted to 3 p.m. to 5 p.m. and 11 a.m. to 2 p.m., respectively, to avoid metabolic interaction between the two drugs. (B) Alcohol self-administration. Animals in the alcohol-primed group began drinking alcohol on day 1 of the paradigm; animals in the alcohol-concurrent group began drinking on day 11. All groups start cocaine self-administration (0.8 mg/kg per infusion) on day 11. The average alcohol intake during the alcohol-priming period was 1 g/kg during the first 5 days, increasing to 1.2 g/kg during the second 5 days. Alcohol intake was similar in the alcohol-primed versus alcohol-concurrent groups from days 11 to 32 [two-way repeated-measures (RM) analysis of variance ...
Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague-Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03 mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25-10 mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5 mg/kg) or saline before 12 consecutive nicotine (0.03 mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03-0.3 mg/kg) and methylphenidate (1.25-10 mg/kg), alone ...
TY - JOUR. T1 - Self-administration of barbiturates and benzodiazepines. T2 - A review. AU - Ator, Nancy A.. AU - Griffiths, Roland R.. PY - 1987/6. Y1 - 1987/6. N2 - Studies of barbiturate and benzodiazepine self-administration are categorized by species and route of administration. Reinforcement, defined as self-administration of drug greater than of a non-drug control, has been demonstrated most often in studies employing the IV route, and there has been greater reliability in this result for a given drug among barbiturates rather than among benzodiazepines. Most studies of PO self-administration in rodents have not demonstrated reinforcement, despite a number of behavioral manipulations to induce drug intake. Studies of PO barbiturate self-administration in monkeys have demonstrated reinforcement but recent studies of PO benzodiazepine self-administration in baboons have not, although physical dependence was demonstrated. Reinforcement via the IG route has not been reliably demonstrated. ...
TY - JOUR. T1 - Methamphetamine self-administration causes persistent striatal dopaminergic alterations and mitigates the deficits caused by a subsequent methamphetamine exposure. AU - McFadden, Lisa M.. AU - Hadlock, Greg C.. AU - Allen, Scott C.. AU - Vieira-Brock, Paula L.. AU - Stout, Kristen A.. AU - Ellis, Jonathan D.. AU - Hoonakker, Amanda J.. AU - Andrenyak, David M.. AU - Nielsen, Shannon M.. AU - Wilkins, Diana G.. AU - Hanson, Glen R.. AU - Fleckenstein, Annette E.. PY - 2012/2/1. Y1 - 2012/2/1. N2 - Preclinical studies have demonstrated that repeated methamphetamine (METH) injections (referred to herein as a "binge" treatment) cause persistent dopaminergic deficits. A few studies have also examined the persistent neurochemical impact of METH self-administration in rats, but with variable results. These latter studies are important because: 1) they have relevance to the study of METH abuse; and 2) the effects of noncontingent METH treatment do not necessarily predict effects of ...
Gene-environment interactions play a significant role in drug abuse and addiction. Epigenetics (the study of how environmental stimuli alter gene expression) has gained attention in recent years as a significant contributor to many behavioral phenotypes of drug addiction. The current study sought to determine if differential rearing conditions can alter a specific epigenetic mechanism, histone deacetylase (HDAC), and how HDAC inhibition can affect drug-taking and drug-seeking behaviors differently among enriched, isolated, or standard-housed rats. Ninety male Sprague-Dawley rats were reared for 30 days in enriched (EC), isolated (IC), or standard (SC) conditions prior to amphetamine (0.03, 0.05, 0.1 mg/kg/infusion, i.v.) self-administration, extinction, or reinstatement sessions. Trichostatin A (TsA; 0.3 mg/kg, i.v.), an HDAC inhibitor, was injected 30 min prior to drug-taking or drug-seeking sessions. Results indicated that EC rats self-administered less amphetamine (0.03 mg/kg/infusion) than ...
Previous examination of binge cocaine self-administration and 2 week withdrawal from cocaine self-administration about ionotropic glutamate receptor subunit (iGluRs) protein levels revealed significant alterations in iGluR protein levels that differed between your mesocorticolimbic and nigrostriatal pathways. and nigrostriatal pathways (substantia nigra SN and dorsal caudate-putamen CPu). Inside the mesolimbic Mouse monoclonal to Histone 3.1. Histones are the structural scaffold for the organization of nuclear DNA into chromatin. Four core histones, H2A,H2B,H3 and H4 are the major components of nucleosome which is the primary building block of chromatin. The histone proteins play essential structural and functional roles in the transition between active and inactive chromatin states. Histone 3.1, an H3 variant that has thus far only been found in mammals, is replication dependent and is associated with tene activation and gene silencing. pathway reductions had been seen in NR1 and GluR5 ...
Ethanol is a psychoactive compound of several beverage abused by humans and it is well known that, as well as other drugs of abuse, increases dopamine (DA) transmission preferentially in the nucleus accumbens (NAc) shell. The aim of our study was to investigate by microdialysis the role of the NAc shell and core DA in the response to ethanol and to ethanol-conditioned stimuli (ethanol-CS) using an instrumental conditioning paradigm with fixed-ratio 1 (FR1). Rats were trained to acquire sucrose and ethanol oral self-administration under a FR 1 paradigm (1 nose poke corresponds to 0.25 ml administration of 20% sucrose or 10% ethanol in 20% sucrose solutions). We found that oral ethanol, either self-administered or given passively, produces an increase of DA transmission in the shell and in the core, strengthened during the self-administration session, while ethanol-CS increased DA preferentially in the NAc shell. Sucrose oral self-administration and its conditioned cues affects DA exclusively in ...
TY - JOUR. T1 - Lateral hypothalamus is required for context-induced reinstatement of extinguished reward seeking. AU - Marchant, N. J.. AU - Hamlin, A.S.. AU - McNally, G. P.. N1 - Imported on 12 Apr 2017 - DigiTool details were: month (773h) = Feb 2009; Journal title (773t) = Journal of Neuroscience. ISSNs: 0270-6474; PY - 2009/2. Y1 - 2009/2. N2 - We studied the role of lateral hypothalamus (LH) in context-induced reinstatement (renewal) of reward seeking. Rats were trained to respond for 4% (v/v) alcoholic beer or 10% (w/v) sucrose reward in one context (Context A) before extinction training in a second context (Context B). On test, rats were returned to the training context, A (ABA), or the extinction context, B (ABB). Return to the training context (ABA) produced robust reinstatement. Reversible inactivation of LH via baclofen/muscimol infusion prevented context-induced reinstatement of beer and sucrose seeking. This prevention was specific to bilateral infusions into LH. We then used the ...
Background 5-HT1B receptor agonists enhance cocaine intake during daily self-administration sessions but decrease cocaine intake when tested after prolonged abstinence. We examined if 5-HT1B receptor agonists produce similar abstinence-dependent effects on methamphetamine intake. Methods Male rats were trained to self-administer methamphetamine (0.1 mg/kg, i.v.) on low (fixed ratio 5 and variable ratio 5) and high (progressive ratio) effort schedules of reinforcement until intake was stable. Rats were then tested for the effects of the selective 5-HT1B receptor agonist, CP 94,253 (5.6 or 10 mg/kg), or the less selective but clinically available 5-HT1B/1D receptor agonist, zolmitriptan (10 mg/kg), on methamphetamine self-administration .... ...
Background 5-HT1B receptor agonists enhance cocaine intake during daily self-administration sessions but decrease cocaine intake when tested after prolonged abstinence. We examined if 5-HT1B receptor agonists produce similar abstinence-dependent effects on methamphetamine intake. Methods Male rats were trained to self-administer methamphetamine (0.1 mg/kg, i.v.) on low (fixed ratio 5 and variable ratio 5) and high (progressive ratio) effort schedules of reinforcement until intake was stable. Rats were then tested for the effects of the selective 5-HT1B receptor agonist, CP 94,253 (5.6 or 10 mg/kg), or the less selective but clinically available 5-HT1B/1D receptor agonist, zolmitriptan (10 mg/kg), on methamphetamine self-administration .... ...
Rationale: D1 dopamine receptor antagonists and agonists attenuate cocaine reinstatement of cocaine-seeking behavior (i.e., responding in the absence of cocaine reinforcement). Objectives: The present
Because peptides are most often labile in the GI tract they are usually administered by injection. The principal fragment of interest, D-Leu-OB-3, has been shown to induce significant weight loss upon i.p injection, nasal administration and oral administration. A non-invasive format is preferred in terms of patient compliance, convenience, ease of self administration, and avoidance of needle stick injuries for patients or care givers. While intranasal administration of protein and peptide drugs has shown some limited success with small peptides such as desmopressin and calcitonin, Aegis Intravail® absorption enhancement agents provide unmatched bioavailabilities - bioavailabilities comparable to injection for small as well as much larger proteins. Our studies have shown that OB-3 peptide formulated with Intravail® excipients induces significant weight loss upon nasal administration with bioavailability comparable to injection approaching or exceeding 100% compared to s.c. injection. Intravail ...
http://www.marketsandmarkets.com/Market-Reports/drug-delivery-technologies-market-1085.html. Drug delivery technologies alter the release of drug so as to facilitate optimum efficacy and safety.Such technologies simplify the dosing regimen and reduce side-effects, thus boosting patient compliance. The global drug delivery market is divided into nine segments, namely, oral, pulmonary, transdermal, injectable, ocular, nasal, topical, implantable,andtransmucosal. Drug delivery technologies have grown phenomenally from plain drug reformulation and release technologies to innovative platforms that hold a huge potential for the effective delivery of biologicals and novel drugs.. The major drivers of this market are patent expiries of certain blockbuster drugs, growing demand for self administration and home healthcare devices, rising incidence of chronic diseases such as cardiovascular diseases, diabetes and cancer, growing focus on pediatric and geriatric patients, and advancing technology.However, ...
If you are seriously impaired your helpers may need to give you glucose gel by rubbing it inside your cheek. Tell them not to put it beyond your teeth in case they get bitten.. If you are unconscious it is important that nothing is administered by mouth in case you choke. Glucagon administration is now necessary. Are all your helpers trained how to use this?. If there is no clear improvement in ten minutes with glucagon they must dial 999 / 911 and get you to hospital. After glucagon administration you can feel very sick indeed. Metoclopramide tablets or injection may be necessary. Your doctor may prescribe this for self administration at these times and if you vomit.. You will also need to build up your glycogen stores by eating your normal diet for 24 hours and meticulously avoiding low blood sugars during this time. You will need to do more frequent testing eg every 2.5 hours instead of the usual pattern and you would correct for lows but not highs.. Children dont have much glycogen to ...
If you are seriously impaired your helpers may need to give you glucose gel by rubbing it inside your cheek. Tell them not to put it beyond your teeth in case they get bitten.. If you are unconscious it is important that nothing is administered by mouth in case you choke. Glucagon administration is now necessary. Are all your helpers trained how to use this?. If there is no clear improvement in ten minutes with glucagon they must dial 999 / 911 and get you to hospital. After glucagon administration you can feel very sick indeed. Metoclopramide tablets or injection may be necessary. Your doctor may prescribe this for self administration at these times and if you vomit.. You will also need to build up your glycogen stores by eating your normal diet for 24 hours and meticulously avoiding low blood sugars during this time. You will need to do more frequent testing eg every 2.5 hours instead of the usual pattern and you would correct for lows but not highs.. Children dont have much glycogen to ...
Dear Editor,. Colitis occurs with exposure to various chemicals, including alcohol, radiocontrast agents, glutaraldehyde, formalin, ergotamine, hydrogen peroxide and drugs (1). Frequency of colitis induced by drugs is often under estimated. Antibiotics, 5-fluorouracil (5-FU), hydroxycarbamide, nonsteroidal anti-inflammatory drugs (NSAIDS) and aspirin are usually incriminated (2-4). We report the case of severe diarrhea and hematochezia after self administration of an indomethacin suppository to a young woman.. Case report. A 30-year-old female presented to the gastroenterology department with rectal pain, diarrhea and rectal bleeding. Her past medical history revealed migraine for 1 year. She had self administered indomethacin suppository 200 mg/day with the hope to improve headache for 3 months. The patient developed severe rectal pain and bloody diarrhea. At admission, physical examination revealed mild abdominal tenderness at lower quadrant and digital rectal examination was painful. ...
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The influence of an external static field applied in the direction of propagation of a high intensity driving laser pulse on the electron trapping in laser wakefield acceleration is explored. It is shown that, in the case of self-injection, the electric charge accelerated can be enhanced in some physical situations.
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Characterization and inhibition of a cholecystokinin-inactivating serine peptidase. Selective inhibition of cocaine-seeking behavior by a partial dopamine D(sub3) receptor agonist
Although these results demonstrate the presence of the α7nACh-NMDA protein complex in rat hippocampal tissue, they do not show whether the α7nACh-NMDAR complex was formed through a direct interaction or indirectly via the involvement of an accessory binding protein. Using in vitro binding assays, we provide evidence that the α7nAChR and NR2A subunits interact directly. As shown in Fig. 2 B (top), an in vitro translated [35S]α7IL2 probe hybridized with GST-NR2ACT but not GST-NR1aCT or GST alone, indicating that a direct protein-protein interaction can occur between the α7nAChR and the NR2A subunit, whereas the association between α7nAChR and NR1a subunits occurred most likely via an interaction between the NR1a and the NR2A subunits. Similarly, the [35S]NR2A probe hybridized with GST-α7IL2 but not GST-α4IL2 or GST alone (Fig. 2 B, bottom), confirming the specificity of the direct protein-protein interaction between α7nACh and NR2A subunit of NMDAR.. To confirm these results and to ...
A powerful drug used in hospitals to prevent deadly irregular heartbeats during heart attacks may benefit potential victims if they are prepared to administer it to themselves, Dutch researchers
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TY - JOUR. T1 - Dopamine Activity in the Nucleus Accumbens During Consummatory Phases of Oral Ethanol Self-Administration. AU - Doyon, William M.. AU - York, Jennifer L.. AU - Diaz, Laurea M.. AU - Samson, Herman H.. AU - Czachowski, Cristine L.. AU - Gonzales, Rueben A.. PY - 2003/10. Y1 - 2003/10. N2 - Background: This present study was designed to clarify the role of dopamine in the nucleus accumbens during operant ethanol self-administration by separating bar pressing (ethanol seeking) from ethanol consumption. Furthermore, we sought to define the relationship between ethanol in the brain and the accumbal dopamine response after oral self-administration of ethanol. Methods: Two separate groups of male Long-Evans rats were trained to bar press with 10% ethanol or water. Rats were trained to elicit an escalating number of bar presses across daily sessions before gaining access to the drinking solution for 20 min. Microdialysis was performed before (during a waiting period), during, and after ...
TY - JOUR. T1 - Cocaine is self-administered into the shell but not the core of the nucleus accumbens of Wistar rats. AU - Rodd, Zachary. AU - McKinzie, David L.. AU - Li, Ting Kai. AU - Murphy, James M.. AU - McBride, William J.. PY - 2002/12/1. Y1 - 2002/12/1. N2 - The rewarding properties of cocaine have been postulated to be regulated, in part, by the mesolimbic dopamine system. However, the possibility that the rewarding properties of cocaine are mediated by direct activation of this system has yielded contradictory findings. The intracranial self-administration technique is used to identify specific brain regions involved in the initiation of response-contingent behaviors for the delivery of a reinforcer. The present study assessed whether adult Wistar rats would self-administer cocaine directly into the nucleus accumbens shell (AcbSh) and core (AcbC). For each subregion, subjects were placed in standard two-lever operant chambers and randomly assigned to one of five groups for each site ...
TY - JOUR. T1 - Self-administration of cocaine increases the release of acetylcholine to a greater extent than response-independent cocaine in the nucleus accumbens of rats. AU - Mark, Gregory. AU - Hajnal, Andras. AU - Kinney, Anthony E.. AU - Keys, Alan S.. PY - 1999. Y1 - 1999. N2 - Rationale: The neurochemical effects of psychostimulant exposure may depend on how these drugs are encountered. A useful method for examining this issue is to compare neurotransmitter release following response-dependent, or self-administered, drug exposure and response-independent exposure. Objectives: This experiment examined the effect of active and passive cocaine administration on acetylcholine (ACh) efflux in the shell region of the nucleus accumbens (NAc) in rats. Methods: One group of rats (CSA: cocaine self-administration) was trained to lever-press for intravenous infusions of cocaine (0.42 mg/kg per infusion) on a fixed-ratio-1 schedule of reinforcement. Cocaine infusions were accompanied by the onset ...
The present study demonstrates that lobeline pretreatment attenuated d-methamphetamine self-administration in rats and that tolerance did not develop rapidly, if at all, to this effect. When administered acutely, lobeline decreased responding for bothd-methamphetamine and sucrose. When administered repeatedly, however, lobeline consistently decreased d-methamphetamine self-administration, with no evidence for development of tolerance in the first 15 min of the session across seven repeated injections. However, examination of the time course revealed that the duration of the lobeline-induced attenuation was longer on day 1 (∼25 min) than on day 7 (∼15 min), suggesting some evidence for the development of tolerance. In contrast, tolerance clearly developed to the lobeline-induced decrease of sucrose reinforced responding. Taken together, these results suggest a specific decrease ind-methamphetamine self-administration following repeated lobeline pretreatment. Furthermore, the lobeline-induced ...
Although naturally produced uric acid has beneficial effects in the body, its accumulation can cause diseases including gout. Rasburicase is a recombinant urate oxidase enzyme used as a drug to help the body to eliminate uric acid. It is typically administered to prevent renal failure during the treatment of tumours. The current formulation involves the lyophilised drug in a preparation suitable only for use in hospitals. A crystalline preparation could permit self administration, avoiding a hospital visit. However, to be suitable for administration by injection, the crystals needs to be smaller than 50 micrometres. Full characterisation of the drugs crystalline polymorphism is required by the health authorities -- this can be carried out by X-ray powder diffraction. There are many added benefits from using a crystalline form of a drug: it permits better control over the release rate into the system by an optimisation of the crystals size and polymorphism, and it should also offer an extended ...
efoods]"This policy would seek to: (1) mitigate illness and prevent death; (2) sustain critical infrastructure; and (3) complement and supplement State, local, territorial, and tribal government medical countermeasure distribution capacity," the order said. "The US Postal Service has the capacity for rapid residential delivery of medical countermeasures for self administration across all communities in the United States," the order added. The US Health and Human Services Secretary Kathleen Sebelius and Homeland Security Secretary Janet Napolitano were instructed to work with the post office to develop a "dispensing model for US cities to respond to a large-scale biological attack, with anthrax as the primary threat consideration." The order calls for the model to be drawn up within 180 days, but gives no details as to whether the idea of using the US postal system to assist Americans in the wake of a biological attack is a new one. The United States has sought to bolster its capacity to respond ...
Initial worsening of signs/symptoms (eg, bone pain, ureteral obstruction, spinal cord compression) may occur; monitor closely in metastatic vertebral lesions, urinary obstruction, hematuria. Monitor serum testosterone, PSA. Increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood glucose, HbA1c, and for signs/symptoms of CVD during therapy. Increased risk of convulsions in patients with history of seizures, epilepsy, cerebrovascular disorder, CNS anomalies or tumors. Risk of QT prolongation in long-term androgen deprivation therapy, congenital long QT syndrome, electrolyte abnormalities (correct and monitor), or CHF; consider monitoring ECGs. Instruct patient on correct self administration. Embryo-fetal toxicity. Pregnancy. Nursing mothers: not recommended. ...
The prelimbic (PL) and infralimbic (IL) medial prefrontal cortex (mPFC) are thought to play opposing roles in drug-seeking behaviour. Specifically, the PL promotes drug-seeking whereas the IL is necessary for the inhibition of drug-seeking during extinction. We studied the roles of the PL, IL and dorsal peduncular PFC (DP) in the expression of context-induced reinstatement, reacquisition and extinction of alcoholic beer-seeking. In context-induced reinstatement (renewal), animals were trained to nosepoke for alcoholic beer (context A), extinguished (context B) and then tested in context A and B. In reacquisition, animals received the same instrumental training and extinction without any contextual manipulation. On test, alcoholic beer was again available and responding was compared with naive controls. Just prior to the test, rats received bilateral infusion of baclofen/muscimol into the PL, IL or DP. Reversible inactivation of the PL attenuated ABA renewal but augmented reacquisition. ...
Protein interacting with C-kinase 1 (PICK1) is a widely expressed scaffold protein known to interact via its PSD-95/discs-large/ZO-1 (PDZ)-domain with several membrane proteins including the dopamine (DA) transporter (DAT), the primary target for cocaines reinforcing actions. Here, we establish the importance of PICK1 for behavioral effects observed after both acute and repeated administration of cocaine. In PICK1 knock-out (KO) mice, the acute locomotor response to a single injection of cocaine was markedly attenuated. Moreover, in support of a role for PICK1 in neuroadaptive changes induced by cocaine, we observed diminished cocaine intake in a self-administration paradigm. Reduced behavioral effects of cocaine were not associated with decreased striatal DAT distribution and most likely not caused by the ∼30% reduction in synaptosomal DA uptake observed in PICK1 KO mice. The PICK1 KO mice demonstrated preserved behavioral responses to DA receptor agonists supporting intact downstream DA ...
The aim of this study was to compare self-administration with face-to-face interview in the investigation of low back pain in adolescents. Fifty-seven adolescents with low back pain (mean age 17.3 y; range 16-18) first completed a questionnaire and were then invited to an interview. Analysis included item completion, percentages of agreement and weighted kappa. Item completion rates were high and comparable between self-administration and interview. Information between both methods was analogous for severity and localization of problems, sleep behaviour, medical consultation and sports/leisure activities. Onset, progression, duration of low back pain and some items on the influence of movement/positions presented less comparable data. Conclusion: Even when two different methods of data acquisition are used, results suggest that the method used does not change the interpretation of results in the case of most items ...