Abstract
It was previously observed that the corticosteroid synthesis inhibitor, aminoglutethimide (AG), markedly facilitates lateral hypothalamic self-stimulation (LHSS) in food-restricted rats. This effect is not present 30 min after injection when plasma corticosterone levels are suppressed, but rather at 2 h when corticosterone has recovered from suppression. In experiment 1, it was confirmed that AG (50.0 mg/kg, SC) lowers the threshold for LHSS in food-restricted rats but not in control rats that have ad libitum access to food. This effect occurred independently of whether food restriction, by itself, lowered threshold. Experiment 2 examined whether the facilitation of LHSS coincides with biosynthetic rebound of corticosteroid precursors. While a pregnenolone surge was demonstrated by radioimmunoassay, dose-response testing with exogenous pregnenolone and progesterone (0.1, 1.0 and 10.0 mg/kg, SC) failed to confirm the prediction that one of these precursors facilitates reward. Therefore, a general test of the involvement of adrenocortical biosynthetic events was conducted in experiment 3 where rats were adrenalectomized (ADX) or sham-operated prior to food restriction. Surprisingly, ADX did not diminish the effect of AG. This finding raises the possibility of a CNS, rather than adrenal, site of action. AG is known to penetrate the blood-brain barrier and exert weak anticonvulsant effects. The facilitation of reward may result from central inhibitory effects of the drug and share a common basis with the enhanced reinforcing potency of other CNS depressants in food- restricted rats.
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Received: 25 March 1997 / Final version: 2 June 1997
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Abrahamsen, G., Kandawire, M. & Carr, K. Aminoglutethimide, a corticosteroid synthesis inhibitor, facilitates brain stimulation reward in food-restricted rats: an investigation of underlying mechanisms. Psychopharmacology 133, 405–412 (1997). https://doi.org/10.1007/s002130050421
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DOI: https://doi.org/10.1007/s002130050421