The effects of ventral tegmental administration of GABA(A), GABA(B), NMDA and AMPA receptor agonists on ventral pallidum self-stimulation.
The ventral pallidum (VP) is a basal forebrain structure that is interconnected with motor and limbic structures and may be considered as an interface between motivational and effector neural signals. Results from a considerable number of studies suggest that this structure is critically involved in reward-related behavior. The VP shares reciprocal connections with other reward-implicated regions, such as the ventral tegmental area (VTA). This anatomy predicts that drug-induced neuronal alterations in the VTA could profoundly alter the function of the VP. Here, using the curve-shift intracranial self-stimulation method, we studied the effects of muscimol (GABA(A) agonist), baclofen (GABA(B) agonist), NMDA and AMPA, microinjected bilaterally into the VTA on the rewarding efficacy of VP self-stimulation. Central injections of the highest dose of muscimol (0.128 microg) resulted in significant elevations in VP self-stimulation thresholds, indicating a reduction in the rewarding efficacy of the stimulation. Elevations in VP self-stimulation thresholds were also evident after intrategmental injections of higher doses of baclofen (0.12, 0.48 microg). By contrast, intrategmental activation of NMDA and AMPA receptors did not affect reward thresholds. These findings suggest that GABAergic and glutamatergic transmission in the VTA activate different circuits that may mediate different functions. Thus, the VTA--VP projection activated by GABA modulates VP stimulation reward, while the projection activated by glutamate may be involved in reward-unrelated effects, rather than in the processing of reward. The decreased rewarding efficacy of VP self-stimulation following intrategmental injections of muscimol and baclofen may be due to GABAergic modulation of ventral tegmental dopaminergic and nondopaminergic neurons projecting to the VP.
Panagis
George
G
University of Crete, School of Social Sciences, Department of Psychology, Crete, Rethymnon, Greece. panagis@psy.soc.uoc.gr
Kastellakis
Andreas
A
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology; D004567:Electrodes, Implanted; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D005917:Globus Pallidus / Q000033:anatomy & histology / Q000502:physiology*; D008297:Male; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000033:anatomy & histology / Q000502:physiology*
D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol; D001418:Baclofen