The effects of ventral tegmental administration of GABAA, GABAB and NMDA receptor agonists on medial forebrain bundle self-stimulation.

Using a conditioned discrimination ICSS paradigm, rate-current intensity functions were determined for both reward- and nonreward-associated responding for electrical self-stimulation of the MFB following intra-VTA infusion of baclofen, muscimol and N-methyl-D,L-aspartate (NMDLA). A low dose (0.064 microgram/0.5 microliter) of the GABAB receptor agonist, baclofen, microinjected into the VTA, ipsilateral to the lateral hypothalamic stimulating electrode, resulted in a rightward shift of the ICSS curve without significantly influencing either maximal rates of operant responding for electrical brain stimulation or nonreinforced performance levels. Increases in MFB current thresholds were also evident after infusion of higher doses of baclofen (0.128, 0.26 and 0.52 microgram) into the ventral tegmentum. Intra-VTA administration of the GABAA receptor agonist, muscimol (0.006, 0.012, 0.025 and 0.05 microgram) and NMDA receptor activation by NMDLA (0.5, 1, 2 and 5 micrograms) did not affect reward thresholds; however, the low dose of muscimol and the high dose of NMDLA elicited behavioral activation resulting in reward-unrelated performance effects. These results implicate the specific involvement of the GABAB receptor in the reward neurocircuitry of the VTA.