Gabaergic and Enkephalinergic Regulation of Locomotion in the Ventral Pallidum: Involvement of the Mesolimbic Dopamine System

Abstract

It is well established that the mesolimbic dopamine projection from the AlO dopamine region in the ventromedial mesencephalon to the nucleus accumbens is important in mediating spontaneous and psychostimulant — induced locomotion (Fink and Smith, 1980; Koob et al., 1981; Clarke et al., 1988). The nucleus accumbens has a dense projection to the ventral pallidum (Nauta et al., 1978; Mogenson et al., 1983; Heimer et al., 1987; Churchill et al., 1990) which utilizes both GABA and enkephalin as neurotransmitters (Walaas and Fonnum, 1979; Zahm et al., 1985). Modulation of this projection to the ventral pallidum by dopamine in the nucleus accumbens mediates dopamine-dependent locomotion. Thus, locomotion elicited by stimulation of dopamine receptors in the nucleus accumbens is abolished following a lesion of the ventral pallidum (Swerdlow et al., 1984a). A role for GABA transmission in the accumbens-ventral pallidal pathway has been shown by the observation that stimulation of GABAa receptors in the ventral pallidum blocks motor activity produced by dopamine agonist injection into the nucleus accumbens (Jones and Mogenson, 1980; Mogenson and Nielsen, 1983; Swerdlow et al., 1984b; Austin and Kalivas, 1988). More recently, it was found that locomotion elicited by microinjection of other neurotransmitter agonists or antagonists into the nucleus accumbens, including a mu opioid agonist, GABAa antagonist, nicotinic agonist and glutamate agonist, is also blocked by muscimol injection into the ventral pallidum (Austin and Kalivas, 1989; Shreve and Uretsky, 1988). Therefore, it appears that locomotion elicited pharmacologically from the nucleus accumbens involves modulation of a GABAergic projection to the ventral pallidum, regardless of the neurochemical stimulus.