3.4.2.3. Kappa Receptors
Much of what is known about the effects of androgens on kappa receptors is derived from a single investigation. In intact male rats, chronic treatment with nandrolone decreases kappa opioid receptors in most brain regions, with significant decreases observed in the nucleus accumbens shell, hypothalamus, central amygdaloid nucleus, lateral globus pallidus, and stria terminalis (Magnusson et al., 2009). In contrast, chronic nandrolone treatment increases kappa receptor density in the caudate putamen and dorsal endopiriform (Magnusson et al., 2009, also see Ruka et al., 2015 for the effects of castration on hypothalamic brain slices). In most of these regions, androgen-induced decreases in kappa receptor density can be explained, in part, as compensatory responses to androgen-induced increases in endogenous dynorphin concentrations. One notable exception is the nucleus accumbens, which exhibits decreases in both dynorphin concentrations and kappa opioid receptor density following androgenic treatment. As noted above (Section 3.4.1), dynorphin negatively modulates dopamine release in the nucleus accumbens, which is critically involved in motivated behavior and drug addiction. Consequently, androgen-induced decreases in kappa opioid signaling in the nucleus accumbens could account, in part, for the positive-reinforcing and abuse-related effects of AAS in human populations.