In vivo microdialysis was used to assess the involvement of ventral tegmental area (VTA) mu, delta, and kappa opioid recep-tors in modulation of basal extracellular ventral stnatal dopamine (DA) and DA-metabolite concentrations. Independent groups of chloral hydrate-anesthetized rats were given VTA microinjections of selective oploid agonists, and extracellular ventral striatal DA and DA-metabolite concentrations were assayed using HPLC. VTA microinjections of ED-Ala2, N-Me-Phe4-Gl-ol]-enkeph-aIm (DAMGO; a mu agonist) and [D-Pen2, D-Pen5]-enkephalin (DDDPE; a delta agonist) each caused dose-orderly increases in ventral striatal DA and DA-metabolite concentrations. The effec-tive concentrations of DPDPE were 1 00-to 1 000-fold higher than the effective concentrations of DAMGO. VTA microin-jections of (transdl)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidi-nyl) cyclo-hexyl]-benzeneacetamide) methane sulfonate hydrate (U-50,488 H); a kappa agonist) failed to alter ventral striatal DA concentrations at any dose tested, but subsequent systemic injections significantly decreased DA and DA-metabolite concentrations. Pretreatment with VTA microinjections of 17-cyclopropylmethyl-6, 7-dehydro-4, 5-epoxy-3, 1 4-dihydroxy-6, 7, 2’, 3’-in-dolmorphinan hydrochloride(naltrindole; a delta antagonist)(delta antagonist) antagonized VTA DPDPE-mediated increases in ventral stnatal DA and DA-metabolite concentrations but failed to antagonize VTA DAMGO-mediated increases. Pretreatment with D-Pen-Cys-Tyr-D-Trp-Om-Thr-Pen-Thr-NH2(CTOP; a mu antagonist) antagonized VTA DAMGO-mediated increases but failed to antagonize VTA DPDPE-mediated increases. Thus both mu and delta receptor agonists appear capable of increasing ventral stnatal DA and DA-metabolite concentrations through selective actions on their preferred class of opioid receptors in the VTA. The increases in ventral striatal DA and DA-metabolite concentrations that are seen after systemic treatment with kappa opioid agonists appear not to involve VTA oploid receptors.

Opiates produce locomotion, they are self-administered and they establish conditioned preferences for environments associated with prior drug exposure(for reviews, see Wise, 1988; Wise, 1989). Opioid receptors in the VTA have been implicated in each of these actions(for reviews, see Bozarth, 1983; Bozarth and Wise, 1983; Wise and Hoffman, 1992). Bilateral VTA microinjections of morphine(Joyce and Iversen, 1979) or-