The effects of intravenous self-administration of 30 μg infusions of either heroin or cocaine, or saline on the concentrations of β-endorphin-immunoreactivity (βE-IR) in the anterior part of the rat brain limbic system were studied. Self-administration of heroin and cocaine for 5 daily sessions resulted in a marked reduction of the concentrations of βE-IR in the nucleus accumbens, rostral striatum, septum and hippocampus at the time of the scheduled next session on day 6. In pooled extracts of these regions from rats receiving saline, combined application of high-pressure liquid chromatography (HPLC) fractionation and specific radioimmunoassays revealed the presence of a number of βE-related peptides co-chromatographing with synthetic non-acetylated and acetylated α, β- and γ-type endorphins. Similar profiles were found after HPLC fractionation of extracts of these regions from rats self-administering heroin and cocaine. Rats self-administering heroin or cocaine, however, showed decreased amounts of all detected forms of β-endorphin as compared to saline rats. These findings indicate that both self-administration of an opiate that induces psychic as well as physical dependence and of a non-opiate stimulant inducing psychic but not physical dependence, results in a significant decrease of βE and related peptides in limbic brain regions of the rat. All forms of βE detected after HPLC were equally affected, suggesting an overall effect of the drugs on peptide turnover. These results suggest that βE and related peptides may be involved in the neurochemical mechanisms underlying psychic dependence to drug
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