A hypothalamic endorphinic lesion attenuates acquisition of cocaine self-administration in the rat.

The present study explores the role of beta-endorphin-producing neurons of the arcuate nucleus in the behavioral effects of cocaine (i.e. acquisition of cocaine self-administration). Eight-week-old female rats were treated with a single estradiol valerate injection that causes a progressive lesion that is specific to beta-endorphin-producing neurons throughout the arcuate nucleus. Cocaine acquisition was suppressed following estradiol valerate pretreatment, while water reinforced behavior was similar to controls. Since estradiol valerate treated rats exhibit low estrogen plasma levels, estrogen replacement was performed but cocaine self-administration acquisition remained suppressed. In addition, analysis of beta-endorphin, dopamine, and DOPAC tissue levels confirmed the specificity of the endorphinic lesion resulting from estradiol valerate treatment. The suppression of cocaine self-administration acquisition following estradiol valerate treatment provides evidence for a significant role for beta-endorphin in cocaine reward.