CHRONIC ETHANOL ADMINISTRATION ALTERS ACTIVITY IN VENTRAL TEGMENTAL AREA NEURONS AFTER CESSATION OF WITHDRAWAL HYPEREXCITABILITY

The present study investigated the activity of neurons in the mesolimb ic dopamine system after the end of the acute phase of the behavioural signs of ethanol withdrawal in mice. This was designed to provide a c omparison with earlier behavioural studies, in which greater developme nt of sensitisation to amphetamine and cocaine, but no change in the i nitial effects of these compounds, or in the behaviour in the absence of drug treatment, was seen when repeated injection of these psychosti mulants were given after chronic ethanol consumption. In the present s tudy, single unit recordings were made from dopamine-sensitive neurons in the ventral tegmental area in perfused midbrain slices prepared 24 h after cessation of chronic ethanol consumption. Profound decreases in firing of the ventral tegmental area (VTA) neurons were seen in sli ces prepared after the ethanol treatment. Firing rates increased after application of N-methyl-DL-aspartate, but still remained lower and mo re variable after the ethanol treatment. Application of dopamine or am phetamine, following stimulation of firing with a low concentration of N-methyl-DL-aspartate, also resulted in lower firing rates in slices from ethanol-treated mice. No changes were seen in release of tritiate d dopamine, in response to applied KCl or amphetamine, from slices of striatum or cerebral cortex, prepared 24 h after cessation of the chro nic ethanol consumption, compared with control values. The results dem onstrate that very substantial decreases in firing rate, and in the nu mber of active cells, occur in VTA neurons at a time when withdrawal h yperexcitability was no longer apparent and overt changes in behaviour were not seen. (C) 1998 Elsevier Science B.V. All rights reserved.