ETHANOL ACTS VIA THE VENTRAL TEGMENTAL AREA TO INFLUENCE HIPPOCAMPAL PHYSIOLOGY

Ethanol selectively alters hippocampal dentate physiology, in part by increasing recurrent inhibition and suppressing long-term potentiation (LTP), a result of ethanol modulation of subcortical inputs. One of t hese inputs includes the ventral tegmental area (VTA) in the midbrain, whose neurons have been shown to discharge faster following systemic ethanol. To further understand how subcortical inputs regulate hippoca mpal physiology and their modulation by ethanol, we studied the effect s of acute intoxicating levels of ethanol on VTA facilitation of the p erforant path to dentate (PPD) responses. Furthermore, to test the rol e of the VTA on known pharmacological effects of ethanol on hippocampa l physiology, we studied the effects of disruption of the VTA-dentate inpute on ethanol actions on recurrent inhibition. Stimulation of the perforant path produced well-characterized evoked responses in the ips ilateral dentate gyrus. Whereas VTA stimulation had no effect on PPD p opulation EPSPs, VTA conditioning markedly increased perforant path-ev oked PS amplitudes (140%). The maximum facilitation was observed at VT A conditioning intervals of 30-40 ms. PS amplitudes returned to baseli ne levels immediately following cessation of VTA conditioning. Intrape ritoneal injections of ethanol (1.2 g/kg) markedly decreased VTA facil itation of PPD PS amplitudes. Lesions of the VTA blocked the ethanol-m ediated increase in PPD paired-pulse inhibition. These results demonst rate that, to a great extent, the effects of intoxicating doses of eth anol on hippocampal physiology are mediated by remote pharmacological effects on the ventral tegmental area, whose direct or indirect influe nces on dentate physiology are described. (C) 1994 Wiley-Liss, Inc.