Effects of d-amphetamine, chlorpromazine, and chlordiazepoxide on intercurrent behavior during spaced-responding schedules.
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Effects of d-amphetamine, chlorpromazine, and chlordiazepoxide on lever pressing under direct control of spaced-responding schedules were compared with effects on intercurrent drinking and wheel running in the rat. Drug effects on lever pressing were systematically related to dose and were consistent for all animals; drug effects on intercurrent behavior were generally different for each animal. In the case of lever presses, increasing doses of d-amphetamine first increased and then decreased response rate, increasing doses of chlorpromazine produced graded decreases in response rate, and doses of chlordiazepoxide up to 40 mg/kg produced no effect on response rate. These data are discussed in context with the concept of schedule control, and it is suggested that the behavioral pharmacology of intercurrent behavior be explored as a useful procedure in the experimental analysis of intercurrent behavior. (+info)
1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.
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Inappropriate activation of the renin-angiotensin system, which plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis, may represent a major risk factor for hypertension, heart attack, and stroke. Mounting evidence from clinical studies has demonstrated an inverse relationship between circulating vitamin D levels and the blood pressure and/or plasma renin activity, but the mechanism is not understood. We show here that renin expression and plasma angiotensin II production were increased severalfold in vitamin D receptor-null (VDR-null) mice, leading to hypertension, cardiac hypertrophy, and increased water intake. However, the salt- and volume-sensing mechanisms that control renin synthesis are still intact in the mutant mice. In wild-type mice, inhibition of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] synthesis also led to an increase in renin expression, whereas 1,25(OH)(2)D(3) injection led to renin suppression. We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH)(2)D(3) markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures. Hence, 1,25(OH)(2)D(3) is a novel negative endocrine regulator of the renin-angiotensin system. Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension. (+info)
The effect of chronic ethanol consumption and withdrawal on mu-opioid and dopamine D(1) and D(2) receptor density in Fawn-Hooded rat brain.
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Previous studies have implicated the dopamine and opioid systems in the induction and maintenance of ethanol consumption. This study investigated, in alcohol-preferring Fawn-Hooded (FH) rats, whether chronic free-choice ethanol consumption and subsequent withdrawal cause alterations in central mu-opioid, dopamine D(1), and D(2) receptor density using autoradiography. FH rats were given a free choice between a 5% ethanol solution and tap water (n = 25) and displayed a mean ethanol consumption of 5.6 g/kg/day. A parallel group of FH rats (n = 5) only had access to tap water. Rats were then withdrawn from ethanol for 0, 1, 2, 5, or 10 days and killed by cervical dislocation and decapitation. Increases in mu-opioid receptor density were observed in the nucleus accumbens and ventral tegmental area upon withdrawal compared with the ethanol naive group. In the lateral amygdala, binding in all withdrawal groups was significantly different from the ethanol naive FH rats, and also from the chronic ethanol rats. An increase in dopamine D(1) receptor density was observed in the substantia nigra, pars reticulata in the 5- and 10-day withdrawal groups compared with ethanol naive. Accumbal dopamine D(2) receptor density (+25-30%) increased in the 10-day withdrawal group compared with both naive and chronic ethanol groups. These findings demonstrate that the opioid and dopamine systems are susceptible to modulation by chronic ethanol consumption and withdrawal in the FH rat. Furthermore, although acute ethanol withdrawal results in modulation of mu-opioid receptors, effects on dopamine receptors are delayed and only become evident 5 to 10 days after withdrawal. (+info)
The maintenance diets of C57BL/6J and 129X1/SvJ mice influence their taste solution preferences: implications for large-scale phenotyping projects.
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We examined the extent to which maintenance diet influences the taste preferences of mice. C57BL/6J (B6) and 129X1/SvJ (129) mice were fed one of three standard cereal-based diets (Teklad 8604, Zeigler NIH-07, Purina 5001), a cereal-based diet formulated for breeding (Purina 5015), or two purified diets (AIN-76A or AIN-93G). The mice were given 48-h two-bottle choice tests between water and the following seven taste solutions: 2 mmol/L saccharin, 5 mmol/L citric acid, 50 mmol/L citric acid, 30 micro mol/L quinine hydrochloride (QHCl), 300 micro mol/L QHCl, 75 mmol/L NaCl, and 10% ethanol. There were very few differences in taste solution preference scores among mice of the same strain fed the three different versions of standard cereal-based diet. There were also very few differences in taste solution preference scores between mice of the same strain fed the two purified diets. However, the mice fed standard cereal-based diets generally drank more water and total fluid than did mice fed purified diets. There were larger differences between the B6 and 129 strains in saccharin and ethanol preference scores with mice fed standard cereal-based diets than purified diets. Conversely, there were larger differences between the B6 and 129 strains in citric acid and NaCl preference scores with mice fed purified diets than standard cereal-based diets. These results show that maintenance diet composition can have strain-dependent effects on taste solution preference. They illustrate that attention must be paid to the effects of diet on phenotype in screens of mutagenized mice and other genetic studies. (+info)
Limbic thalamic lesions, appetitively motivated discrimination learning, and training-induced neuronal activity in rabbits.
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A substantial literature implicates the anterior and mediodorsal (limbic) thalamic nuclei and the reciprocally interconnected areas of cingulate cortex in learning, memory, and attentional processes. Previous studies have shown that limbic thalamic lesions severely impair discriminative avoidance learning and that they block development of training-induced neuronal activity in the cingulate cortex. The present study investigated the possibility that the limbic thalamus and cingulate cortex are involved in reward-based discriminative approach learning, wherein head-extension responses yielding oral contact with a drinking spout that was inserted into the conditioning chamber after a positive conditional stimulus (CS+) were reinforced with a water reward but responses to the spout after a negative conditional stimulus (CS-) were not reinforced. In this task, the rabbits learned primarily to omit their prepotent responses to the spout on CS- trials. Acquisition was severely impaired in rabbits given limbic thalamic lesions before training. As during avoidance learning, posterior cingulate cortical neurons of control rabbits developed learning-related neuronal responses to task-relevant stimuli, but this activity was severely attenuated in rabbits with lesions. These results support a general involvement of the cingulothalamic circuitry in instrumental approach and avoidance learning. The fact that learning consisted of response omission indicated that the cingulothalamic role is not limited to acquisition or production of active behavioral responses, such as locomotion. It is proposed that cingulothalamic neurons mediate associative attention, wherein enhanced neuronal responses to stimuli associated with reinforcement facilitate the selection and production of task-relevant responses. (+info)
Circadian differences in stress-induced pressor reactivity in mice.
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The objective of this study was to determine the effect of chronic stress exposure on the circadian pattern of cardiovascular responses in mice. Using male C57BL6 mice with carotid arterial catheters, we tested the effect of 7 days of intermittent shaker stress on body weight, food intake, drinking activity, plasma corticosterone, mean arterial pressure (MAP), and heart rate. The stress was delivered automatically for 2-minute periods (150 cycles/min), 45 times/d for 7 days. Plasma corticosterone was significantly increased in acutely and chronically stressed mice, with a partial attenuation in the chronic condition. Stress increased water intake, produced no change in food intake, and significantly decreased body weight (5% change). MAP and heart rate were measured continuously on stress days 1, 3, and 7 and during the basal and recovery periods. Chronic stress did not produce a sustained increase in MAP; however, there was an increase in MAP during the first stress day and a decrease during the recovery period. There was a circadian pattern in the pressor responses, with greater increases seen during the light period (nonactive phase) than in the dark period (+24% versus +11% on stress day 3, light versus dark). The results suggest that a stress delivered during the nonactive phase represents a higher cardiovascular risk. (+info)
Superoxide mediates the actions of angiotensin II in the central nervous system.
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Angiotensin II (Ang II) has profound effects in the central nervous system (CNS), including promotion of thirst, regulation of vasopressin secretion, and modulation of sympathetic outflow. Despite its importance in cardiovascular and volume homeostasis, angiotensinergic mechanisms are incompletely understood in the CNS. Recently, a novel signaling mechanism for Ang II involving reactive oxygen species (ROS) has been identified in a variety of peripheral tissues, but the involvement of ROS as second messengers in Ang II-mediated signaling in the CNS has not been reported. The hypothesis that superoxide is a key mediator of the actions of Ang II in the CNS was tested in mice using adenoviral vector-mediated expression of superoxide dismutase (AdSOD). Changes in blood pressure, heart rate, and drinking elicited by injection of Ang II in the CNS were abolished by prior treatment with AdSOD in the brain, whereas the cardiovascular responses to carbachol, another central vasopressor agent, were unaffected. In addition, Ang II stimulated superoxide generation in primary CNS cell cultures, and this was prevented by the Ang II receptor (Ang II type 1 subtype) antagonist losartan or AdSOD. These results identify a novel signaling mechanism mediating the actions of Ang II in the CNS. Dysregulation of this signaling cascade may be important in hypertension and heart failure triggered by Ang II acting in the CNS. (+info)
Effects of haloperidol on schedule-induced polydipsia.
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In dose-related amounts, the drug haloperidol attenuated schedule-induced drinking by rats prefed with 0.01-mg drug added to 0, 25, 50, 75 or all of 100 Noyes 45-mg pellets. Drug pellets also induced less drinking than did regular Noyes pellets by rats that obtained these pellets at 1-min intervals by bar pressing. Haloperidol also reduced bar pressing and, temporarily, rate of reinforcement. The results appeared not to be due to a general sedative effect of haloperidol but to its selective power to reduce angiotensin-induced drinking. Thus, schedule-induced drinking, which is abnormal in not causing satiation, is controllable by a drug that interferes with the renin-angiotensin hormone system thought to regulate normal drinking. (+info)