Facilitation of self-stimulation of ventral tegmentum by microinjection of opioid receptor subtype agonists.

ABSTRACT

Intracranial self-stimulation (ICSS) evoked from the ventral tegmental area-substantia nigra (VTA-SN) and lateral hypothalamus-medial forebrain bundle (LH-MFB) was assessed following microinjections of mu (Tyr-D-Ala2-N-Me-Phe4-Gly5ol DAGO), delta-(D-Ala2, D-Met5)-enkephalin DADME) or kappa (Dynorphin-B or Rimorphin) opioid receptor subtype agonists or saline into either VTA-SN or LH-MFB. The current intensity was fixed at an optimum level to obtain 60-70% of the maximum asymptotic response rate. DAGO (5 micrograms/0.5 microliters), DADME (2 micrograms/0.5 microliters) or Dynorphin B (0.5 microgram/0.5 microliters) injected into VTA-SN facilitated the self-stimulation rates of VTA-SN by 27%, 32%, and 59%, respectively. These microinjections did not alter the self-stimulation of LH-MFB when effects of these injections were still persisting in VTA-SN. Similar doses of these opioid receptor agonists injected into LH-MFB had no significant effect on the self-stimulation rates of either LH-MFB or VTA-SN. The facilitatory effects of DADME were completely abolished by naloxone (30 mg/kg IP). Taken together, these results suggest that all three opioid receptor subtypes of ventral tegmentum and not of lateral hypothalamus are involved in the electrically evoked self-stimulation of VTA-SN.