Methodological Considerations

Although most studies examining the effects of adrenalectomy on the behavioral responses to drugs are consistent, some studies have not observed decreased drug effects following ablation of the adrenal glands. For example, as mentioned previously, adrenalectomy does not decrease sensitization to the locomotor effects of cocaine when it is performed after a sensitizing paradigm (18,19). In addition, adrenalectomy does not reduce cocaine facilitation of brain stimulation (46) or drug-induced reinstatement of seeking behavior (for review, see ref. 43). The nature of this discrepancy is unclear. However, it is important to point out that corticosterone levels at the time of adrenalectomy (i.e., circulating levels of corticosterone at the time when the adrenal glands are removed) could play a fundamental role in determining whether adrenalectomy will or not reduce drug effects. Thus, it has been shown (12,47) that adrenalectomy has no effects on the locomotor response to cocaine or on the analgesic effects of morphine if it is performed when corticosterone levels are elevated, such as during the dark phase, following stress, an injection of corticosterone, or when animals are anesthetized with pentobarbital (because of the longer induction of anesthesia with barbiturates, adrenals are removed several minutes after the animals have been removed from the colony room—a time long enough for corticosterone levels to rise). Adrenalectomy seems most efficient in reducing drug effects when levels of the hormone are low, that is, when it is performed rapidly, under inhalant anesthetics (12,47). Although the mechanisms underlying this state-dependent effect of adrenalectomy are not known, it is likely that this effect could explain, at least in part, the discrepancies in the literature. For example, it is possible that high levels of corticosterone after withdrawal from drug self-administration could prevent the effects of adrenalectomy on drug-induced reinstatement of seeking behavior, or that removing the adrenal glands during a drug-sensitizing paradigm (when levels of the hormone are elevated) could also prevent the locomotor-suppressing effects of adrenalectomy.

Drug Addiction Report

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