Reevaluation of the Effects of Castration on Naloxone-Sensitive Opiate Receptors in the Male Rat Brain

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Abstract
There is a great deal of conflicting data regarding the issue of whether androgens influence opiate receptors in the whole male rat brain. Although Hahn and Fishman initially reported that long-term castration produced a large increase in the density of opiate-binding sites, relative to controls, no other independent group has been able to replicate these results. Recently, the former investigators reported that procedural differences could fully account for the discrepancies in the literature. Because of the importance of demonstrating a direct biochemical association between steroid- and endogenous opioid-containing neuronal elements in brain, we have reexamined the issue of whether long-term castration influences opiate receptors in whole male rat brain. To accomplish this goal, we incorporated all of the critical procedural variables which were identified by Hahn and Fishman as possible confounding variables in such studies. Our results clearly demonstrate that under identical conditions, we were unable to replicate the results of these investigators. In addition, we attempted to use other paradigms in an attempt to resolve this long-standing controversy in the literature, but these attempts were also unsuccessful. We are unable to explain our inability to replicate the results of Hahn and Fishman. However, it should be noted that at least 4 independent groups have now failed to reproduce their findings. Thus, it appears that the intrinsically attractive hypothesis that steroids influence opiate receptors cannot be addressed using whole brain analysis or relatively crude areas of brain and relatively nonspecific opiate ligands. Rather, it seems probable that this issue can only be addressed using techniques which recognize the marked regional localization of steroid effects and multiple opioid receptor subtypes in brain (e.g. autoradiography).