Self-administration of morphine, DAMGO, and DPDPE into the ventral tegmental area of rats.

Intracranial self-administration of mu- and delta-opioid agonists was demonstrated in male Long-Evans rats. Independent groups were allowed to lever-press for ventral tegmental area (VTA) microinfusions of morphine, the selective mu agonist [D-Ala2,N-Me-Phe4-Gly5-ol]-enkephalin (DAMGO), the selective delta-agonist [D-Pen2,D-Pen5]-enkephalin (DPDPE), or ineffective drug vehicle. Morphine, DAMGO, and DPDPE were each effective in establishing and maintaining lever-pressing habits. Lever-pressing responses were extinguished during a session when vehicle was substituted for drug, and reinstated when drug reinforcement was reestablished. Thus, it appears that VTA mu- and delta-opioid receptors are each involved in reinforcement of opiate self-administration. The effective dose of DAMGO--both for establishing and for maintaining the lever-press habit--was 100 times lower than the effective doses for DPDPE and morphine, suggesting that the major contribution of VTA mechanisms to intravenous heroin self-administration involves an action on mu-opioid receptors.