Uri Shalev1, Michela Marinelli2, Michael H Baumann3, Pier-Vincenzo Piazza2, Yavin Shaham4. 1. Behavioral Neuroscience Branch, IRP/NIDA/NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, USA. ushalev@intra.nida.nih.gov. 2. Laboratoire de Psychobiologie des Comportements Adaptatifs, INSERM U.259, Bordeaux, France, France. 3. Medication Discovery Research Branch, IRP/NIDA/NIH, Baltimore, Md., USA, USA. 4. Behavioral Neuroscience Branch, IRP/NIDA/NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, USA.
Abstract
RATIONAL AND OBJECTIVES: Acute 1-day food deprivation stress reinstates heroin seeking in rats, but the generality of this effect to other drugs, and its underlying mechanisms, are largely unknown. Here we studied whether food deprivation would reinstate cocaine seeking and whether the stress hormone, corticosterone, is involved in this effect. METHODS: Rats were trained to press a lever for cocaine for 10-12 days (0.5-1.0 mg/kg per infusion, IV, 4 h/day) and were then divided into four groups that underwent different manipulations of plasma corticosterone levels: (1) bilateral adrenalectomy (ADX) surgery, (2) ADX surgery+50-mg corticosterone pellets (ADX+P), (3) ADX surgery+50-mg corticosterone pellets+4-h access (0800-1200 hours) to corticosterone (50 micro g/ml) dissolved in a drinking solution (ADX+P/W), or (4) sham surgery. Next, rats were given 7-12 days of extinction training (during which lever presses were not reinforced with cocaine), and after reaching an extinction criterion they were tested for reinstatement of cocaine seeking following exposure to 21 h of food deprivation. RESULTS: Food deprivation was found to reinstate cocaine seeking in sham-operated rats, but not in rats in which circulating corticosterone was removed (ADX group). In addition, the effect of food deprivation on reinstatement of cocaine seeking was significantly attenuated in rats maintained on basal diurnal levels of corticosterone (ADX+P group). However, food deprivation reinstated cocaine seeking in rats with limited daily access to additional corticosterone in the drinking water (ADX+P/W group). In this group, corticosterone levels were twice as high as the ADX+P group but were significantly lower than those of sham rats. CONCLUSIONS: The present data, together with previous work on footshock-induced reinstatement of drug seeking, suggest that corticosterone plays a permissive role in stress-induced reinstatement of cocaine seeking, yet its effects are not associated with the stressor-induced increases in plasma corticosterone levels.
RATIONAL AND OBJECTIVES: Acute 1-day food deprivation stress reinstates heroin seeking in rats, but the generality of this effect to other drugs, and its underlying mechanisms, are largely unknown. Here we studied whether food deprivation would reinstate cocaine seeking and whether the stress hormone, corticosterone, is involved in this effect. METHODS:Rats were trained to press a lever for cocaine for 10-12 days (0.5-1.0 mg/kg per infusion, IV, 4 h/day) and were then divided into four groups that underwent different manipulations of plasma corticosterone levels: (1) bilateral adrenalectomy (ADX) surgery, (2) ADX surgery+50-mg corticosterone pellets (ADX+P), (3) ADX surgery+50-mg corticosterone pellets+4-h access (0800-1200 hours) to corticosterone (50 micro g/ml) dissolved in a drinking solution (ADX+P/W), or (4) sham surgery. Next, rats were given 7-12 days of extinction training (during which lever presses were not reinforced with cocaine), and after reaching an extinction criterion they were tested for reinstatement of cocaine seeking following exposure to 21 h of food deprivation. RESULTS:Food deprivation was found to reinstate cocaine seeking in sham-operated rats, but not in rats in which circulating corticosterone was removed (ADX group). In addition, the effect of food deprivation on reinstatement of cocaine seeking was significantly attenuated in rats maintained on basal diurnal levels of corticosterone (ADX+P group). However, food deprivation reinstated cocaine seeking in rats with limited daily access to additional corticosterone in the drinking water (ADX+P/W group). In this group, corticosterone levels were twice as high as the ADX+P group but were significantly lower than those of sham rats. CONCLUSIONS: The present data, together with previous work on footshock-induced reinstatement of drug seeking, suggest that corticosterone plays a permissive role in stress-induced reinstatement of cocaine seeking, yet its effects are not associated with the stressor-induced increases in plasma corticosterone levels.
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