ABSTRACT
Cocaine and amphetamine regulated transcript (CART) has been implicated in the regulation of the stress response. Although the forced swimming test (FST), in which rats are forced to swim for 15 min (pretest swim) and then again for 5 min (test swim) 24 h later, has been used to study the effects of antidepressants, there have been few studies examining the effects of antidepressants on FST-induced changes in CART mRNA levels in the brain. To answer this question, we injected reboxetine and citalopram into male Sprague-Dawley rats 1, 5, and 23.5 h before the test swim and then sacrificed rats 2 h after the test swim, at the peak of the FST-induced increase in CART expression. The FST significantly increased CART mRNA levels in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus 2 h after the test session. Both reboxetine and citalopram pretreatment blocked FST-induced increases in CART mRNA levels in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus, despite the fact these antidepressants exert their therapeutic effect by different mechanisms. In addition, the FST significantly increased plasma corticosterone levels, and this effect was also blocked by reboxetine and citalopram pretreatment. These results suggest that inhibition of FST-induced increases in CART expression in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus may be a common mechanism of antidepressant effects during the FST.
Subject(s)
Adrenergic Uptake Inhibitors/pharmacology , Citalopram/pharmacology , Morpholines/pharmacology , Selective Serotonin Reuptake Inhibitors/pharmacology , Amphetamine/metabolism , Amphetamine/pharmacology , Amygdala/drug effects , Animals , Behavior, Animal/drug effects , Cocaine/metabolism , Cocaine/pharmacology , Corticosterone/blood , Dopamine Uptake Inhibitors/metabolism , Dopamine Uptake Inhibitors/pharmacology , Locus Coeruleus/drug effects , Male , Morpholines/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Nerve Tissue Proteins/pharmacology , Nucleus Accumbens/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Messenger/pharmacology , Rats , Rats, Sprague-Dawley , Reboxetine , Swimming/psychologyABSTRACT
The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces food and water intake is unclear. We examined whether such a food and water intake-reducing single administration of TCDD induced changes in corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent changes in these neuropeptides, male Sprague-Dawley rats were given TCDD (50 microg/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose-dependent changes in feeding and neuropeptides, rats were also given a range of TCDD doses (12.5, 25, or 50 microg/kg) and terminated 14 days later. TCDD suppressed food and water intake over 14 days in a dose-dependent manner. TCDD treatment also increased CRF and POMC mRNA levels in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and time-dependent manner. These increases were related to decreased food intake following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels in the PVN, and these increases were related to decreased water intake. Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to 14 days after TCDD administration. These results suggest that a single administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA levels in the hypothalamus and that these changes are related to reduced food and water intake 7 to 14 days after TCDD administration.
Subject(s)
Drinking/drug effects , Eating/drug effects , Environmental Pollutants/toxicity , Gene Expression Regulation/drug effects , Polychlorinated Dibenzodioxins/toxicity , Animals , Arginine Vasopressin/drug effects , Arginine Vasopressin/metabolism , Corticotropin-Releasing Hormone/drug effects , Corticotropin-Releasing Hormone/metabolism , Dose-Response Relationship, Drug , Environmental Pollutants/administration & dosage , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , Polychlorinated Dibenzodioxins/administration & dosage , Pro-Opiomelanocortin/drug effects , Pro-Opiomelanocortin/metabolism , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
Although growth associated protein-43 (GAP-43) is known to play a significant role in the regulation of axonal growth and the formation of new neuronal connections in the hippocampus, there is only a few studies on the effects of acute stress on GAP-43 mRNA expression in the hippocampus. Moreover, the effects of repeated citalopram treatment on chronic mild stress (CMS)-induced changes in GAP-43 mRNA expression in the hippocampus have not been explored before. To explore this question, male rats were exposed to acute immobilization stress or CMS. Also, citalopram was given prior to stress everyday during CMS procedures. Acute immobilization stress significantly increased GAP-43 mRNA expression in all subfields of the hippocampus, while CMS significantly decreased GAP-43 mRNA expression in the dentate granule cell layer (GCL). Repeated citalopram treatment decreased GAP-43 mRNA expression in the GCL compared with unstressed controls, but this decrease was not further potentiated by CMS exposure. Similar decreases in GAP-43 mRNA expression were observed in CA1, CA3 and CA4 areas of the hippocampus only after repeated citalopram treatment in CMS-exposed rats. This result indicates that GAP-43 mRNA expression in the hippocampus may differently respond to acute and chronic stress, and that repeated citalopram treatment does not change CMS-induced decreases in GAP-43 mRNA expression in the GCL.
