Ethanol exposure differentially alters central monoamine neurotransmission in alcohol-preferring versus -nonpreferring rats. (1/446)

Individual differences in ethanol preference may be linked to differences in the functional activity of forebrain monoamine systems or their sensitivity to modification by ethanol. To test this hypothesis, basal extracellular concentrations of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens as well as the effects of repeated ethanol pretreatment on the basal release of these transmitters were examined in alcohol-preferring (P), alcohol-nonpreferring (NP), and genetically heterogeneous Wistar rats. All animals received i.p. injections of ethanol (1.0 g/kg) or saline for 5 consecutive days. Fifteen hours after the final pretreatment, basal extracellular concentrations and "in vivo extraction fraction" values for DA and 5-HT were determined by no-net-flux in vivo microdialysis. In ethanol-naive rats, significant line differences were observed with high basal 5-HT release in P rats, low 5-HT release in NP rats, and intermediate 5-HT levels in Wistar rats. No differences among groups were noted in basal DA release. Ethanol pretreatment decreased basal extracellular 5-HT levels in P rats whereas increasing 5-HT efflux was seen in the Wistar and NP lines. In addition, ethanol pretreatment increased extracellular DA concentrations in Wistar and P rats, but not in NP rats. The results confirm a relationship between the functional status of forebrain DA and 5-HT systems and ethanol preference or aversion. Moreover, the data suggest that ethanol exposure can alter basal DA and 5-HT in the nucleus accumbens and that vulnerability to ethanol-induced changes in monoamine neurotransmission may be a factor in genetically determined ethanol preference.  (+info)

Improvement by nefiracetam of beta-amyloid-(1-42)-induced learning and memory impairments in rats. (2/446)

1. We have previously demonstrated that continuous i.c.v. infusion of amyloid beta-peptide (A beta), the major constituent of senile plaques in the brains of patients with Alzheimer's disease, results in learning and memory deficits in rats. 2. In the present study, we investigated the effects of nefiracetam [N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384] on A beta-(1-42)-induced learning and memory deficits in rats. 3. In the A beta-(1-42)-infused rats, spontaneous alternation behaviour in a Y-maze task, spatial reference and working memory in a water maze task, and retention of passive avoidance learning were significantly impaired as compared with A beta-(40-1)-infused control rats. 4. Nefiracetam, at a dose range of 1-10 mg kg(-1), improved learning and memory deficits in the A beta-(1-42)-infused rats when it was administered p.o. 1 h before the behavioural tests. 5. Nefiracetam at a dose of 3 mg kg(-1) p.o. increased the activity of choline acetyltransferase in the hippocampus of A beta-(1-42)-infused rats. 6. Nefiracetam increased dopamine turnover in the cerebral cortex and striatum of A beta-(1-42)-infused rats, but failed to affect the noradrenaline, serotonin and 5-hydroxyindoleacetic acid content. 7. These results suggest that nefiracetam may be useful for the treatment of patients with Alzheimer's disease.  (+info)

Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms. (3/446)

We used a novel computerized decision-making task to compare the decision-making behavior of chronic amphetamine abusers, chronic opiate abusers, and patients with focal lesions of orbital prefrontal cortex (PFC) or dorsolateral/medial PFC. We also assessed the effects of reducing central 5-hydroxytryptamine (5-HT) activity using a tryptophan-depleting amino acid drink in normal volunteers. Chronic amphetamine abusers showed suboptimal decisions (correlated with years of abuse), and deliberated for significantly longer before making their choices. The opiate abusers exhibited only the second of these behavioral changes. Importantly, both sub-optimal choices and increased deliberation times were evident in the patients with damage to orbitofrontal PFC but not other sectors of PFC. Qualitatively, the performance of the subjects with lowered plasma tryptophan was similar to that associated with amphetamine abuse, consistent with recent reports of depleted 5-HT in the orbital regions of PFC of methamphetamine abusers. Overall, these data suggest that chronic amphetamine abusers show similar decision-making deficits to those seen after focal damage to orbitofrontal PFC. These deficits may reflect altered neuromodulation of the orbitofrontal PFC and interconnected limbic-striatal systems by both the ascending 5-HT and mesocortical dopamine (DA) projections.  (+info)

Differential c-Fos expression in cholinergic, monoaminergic, and GABAergic cell groups of the pontomesencephalic tegmentum after paradoxical sleep deprivation and recovery. (4/446)

Multiple lines of evidence indicate that neurons within the pontomesencephalic tegmentum are critically involved in the generation of paradoxical sleep (PS). From single-unit recording studies, evidence suggests that unidentified but "possibly" cholinergic tegmental neurons discharge at higher rates during PS than during slow wave sleep or even waking and would thus play an active role, whereas "presumed" monoaminergic neurons cease firing during PS and would thus play a permissive role in PS generation. In the present study performed on rats, c-Fos immunostaining was used as a reflection of neuronal activity and combined with immunostaining for choline acetyltransferase (ChAT), serotonin (Ser), tyrosine hydroxylase (TH), or glutamic acid decarboxylase (GAD) for immunohistochemical identification of active neurons during PS recovery ( approximately 28% of recording time) as compared with PS deprivation (0%) and PS control (approximately 15%) conditions. With PS recovery, there was a significant increase in ChAT+/c-Fos+ cells, a significant decrease in Ser+/c-Fos+ and TH+/c-Fos+ cells, and a significant increase in GAD+/c-Fos+ cells. Across conditions, the percent PS was correlated positively with tegmental cholinergic c-Fos+ cells, negatively with raphe serotonergic and locus coeruleus noradrenergic c-Fos+ cells, and positively with codistributed and neighboring GABAergic c-Fos+ cells. These results support the hypothesis that cholinergic neurons are active, whereas monoaminergic neurons are inactive during PS. They moreover indicate that GABAergic neurons are active during PS and could thus be responsible for inhibiting neighboring monoaminergic neurons that may be essential in the generation of PS.  (+info)

Behavioral and neurochemical alterations evoked by p-Chlorophenylalanine application in rats examined in the light-dark crossing test. (5/446)

The aim of the present study is to examine the effects of serotonin synthesis inhibition with p-Chlorophenylalanine (p-CPA) in rats on (1) anxiety behavior examined in the light-dark crossing test and, (2) regional brain concentration of monoamines (NA, DA and 5-HT) and their metabolites (MHPG, DOPAC, HVA and 5-HIAA) as well as GABA in the hypothalamus, amygdala, hippocampus, midbrain central gray matter and the frontal cortex. Treatment of animals with p-CPA produced a significant increase in time out from the illuminated part of the chamber and in time of locomotor activity in the illuminated part of the chamber. HPLC analysis showed a significant reduction of 5-HT and 5-HIAA concentration in all examined brain regions with the exception of the frontal cortex. Additionally, a significant decrease in DA and its metabolites, DOPAC and HVA occurred in the hypothalamus and amygdala. Moreover, we observed a significant decrease in frontal cortex NA concentration after p-CPA administration. The results of our study suggest that administration of p-CPA is effective in reduction of anxiety through depletion of 5-HT accompanied by diminution of catecholamines, especially DA and its metabolites in the main emotional brain regions.  (+info)

Cerebrospinal fluid monoaminergic metabolites differ in wild anubis and hybrid (Anubis hamadryas) baboons: possible relationships to life history and behavior. (6/446)

The article reports monoaminergic metabolite [homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)], values from the cerebrospinal fluid (CSF) of 27 wild baboons (Papio hamadryas) aged 40 to 140 months. Animals were either anubis, or anubis with hamadryas admixture; males of the latter subspecies generally have a reduced tendency to disperse from their natal groups. Overall, the values and interrelationships among the CSF monoamine metabolites resembled data reported from closely related, captive-housed animals. For example, age was significantly correlated with HVA concentrations (r = -60, p < .05), but not with the other metabolites. Notably, males characterized by hamadryas admixture had significantly higher concentrations of HVA, 5-HIAA, and MHPG (p < .05, respectively), a result possibly driven by differences in serotonergic activity. These data provide initial evidence that variation in central monoaminergic activity, as indicated by CSF monoamine metabolite concentrations, may reflect differences in behavior and life history that have taxonomic and, perhaps, evolutionary significance.  (+info)

Heat shock protein expression protects against cerebral ischemia and monoamine overload in rat heatstroke. (7/446)

This study attempted to ascertain whether the ischemic damage to neurons and monoamine overload in brain that occur during rat heatstroke can be attenuated by heat shock protein (HSP) 72 induction. Effects of heatstroke on mean arterial pressure (MAP), cerebral blood flow (CBF), brain dopamine (DA) and serotonin (5-HT) release, and neural damage score were assayed in rats 0, 16, or 48 h after heat shock (42 degrees C for 15 min) or chemical stress (5 mg/kg sodium arsenite ip). Brain HSP 72 in rats after heat shock or chemical stress was detected by Western blot, and brain monoamine was determined by a microdialysis probe combined with high-performance liquid chromatography. Heatstroke was induced by exposing the animal to a high ambient temperature (43 degrees C); the moment at which MAP and CBF decreased from their peak values was taken as the time of heatstroke onset. Prior heat shock or chemical stress conferred significant protection against heatstroke-induced hyperthermia, arterial hypotension, cerebral ischemia, cerebral DA and 5-HT overload, and neural damage and correlated with expression of HSP 72 in brain at 16 h. However, at 48 h, when HSP 72 expression returned to basal values, the above responses that occurred during the onset of heatstroke were indistinguishable between the two groups (0 h vs. 48 h). These results lead to the hypothesis that the brain can be preconditioned by thermal or chemical injury, that this preconditioning will induce HSP 72, and that HSP 72 induction will correlate quite well with anatomic, histochemical, and hemodynamic protection in rat heatstroke.  (+info)

Sensitization to the effects of tumor necrosis factor-alpha: neuroendocrine, central monoamine, and behavioral variations. (8/446)

Consistent with the proposition that cytokines act as immunotransmitters between the immune system and the brain, systemic administration of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha; 1.0-4.0 microg) induced mild illness in CD-1 mice, increased plasma corticosterone concentrations, and altered central norepinephrine, dopamine, and serotonin turnover. The actions of TNF-alpha were subject to a time-dependent sensitization effect. After reexposure to a subeffective dose of the cytokine (1.0 microgram) 14-28 d after initial treatment, marked illness was evident (reduced consumption of a palatable substance and diminished activity and social exploration), coupled with an elevation of plasma corticosterone levels. In contrast, cytokine reexposure 1-7 d after initial treatment did not elicit illness, and at the 1 d interval the corticosterone response to the cytokine was reduced. The increase of norepinephrine release within the paraventricular nucleus of the hypothalamus, as reflected by elevated accumulation of 3-methoxy-4-hydroxyphenylglycol, was augmented at the longer reexposure intervals. In contrast, within the central amygdala and the prefrontal cortex TNF-alpha reexposure at the 1 d interval was associated with a pronounced sensitization-like effect, which was not apparent at longer intervals. Evidently, systemic TNF-alpha proactively influences the response to subsequent treatment; however, the nature of the effects (i.e., the behavioral, neuroendocrine, and central transmitter alterations) vary over time after initial cytokine treatment. It is suggested that the sensitization may have important repercussions with respect to cognitive effects of TNF-alpha and may also be relevant to analyses of the neuroprotective or neurodestructive actions of cytokines.  (+info)