Facilitatory effect of unilateral lesion of the ventral tegmental area on locomotor response to stimulation of the contralateral ventral tegmental area: involvement of GABAergic transmission

Abstract

It was found previously that in the rat, unilateral electrolytic lesion of the ventral tegmental area (VTA) facilitated feeding induced by electrical stimulation of the homologous VTA tissue in the contralateral hemisphere. In the present work, VTA stimulation-induced locomotor response was tested in male Wistar rats using a latency to move/stimulation frequency curve shift paradigm in order to check for functional generality of the “contralateral facilitation effect” and also with the aim of elaborating an easy and reliable behavioral model to study this phenomenon. In a further step, the hypothesis was tested that enhancement of function of the intact VTA results from elimination of tonic GABAergic influence derived normally from the lesioned VTA. GABA A (bicuculline, doses 0, 0.5 and 5.0 ng) and GABA B (phaclofen, doses 0, 500 and 1000 ng) receptors antagonists, and for comparison, a GABA A receptor agonist (muscimol, doses 0, 12.5, 25.0 and 50.0 ng), were injected unilaterally to VTA and their effect on locomotor response elicited by electrical stimulation of the contralateral VTA was tested in a latency/frequency paradigm. It was found that similar to feeding, locomotor response evoked by unilateral electrical stimulation of the VTA was facilitated after contralateral VTA lesion which manifested as a decrease of the locomotion threshold and a leftward shift of the function relating latency to move to stimulation frequency. The effect was immediate, long-lasting and specific to the VTA destruction; lesions outside the VTA area caused gradual impairment of the locomotor response to stimulation. The facilitatory effect of the electrolytic lesion could be replicated by bicuculline, which significantly facilitated stimulation-induced behavior. Phaclofen exerted slight facilitating influence only at a low dose. No effect of muscimol on the locomotion threshold was found. We conclude that “the contralateral facilitation effect” at the level of VTA reflects the interhemispheric regulation of activity of the dopaminergic (DA) cells in which GABA A-mediated interhemispheric communication plays a significant role.