Prolonged increase in the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol following repeated exposure to cycles of ethanol access and deprivation.

The posterior ventral tegmental area (VTA) is a neuroanatomical substrate mediating the reinforcing effects of ethanol in rats. Repeated alcohol deprivations produce robust ethanol intakes of alcohol-preferring (P) rats during relapse and increase the reinforcing effects of oral alcohol self-administration. The objective of this study was to test the hypothesis that alcohol drinking and repeated alcohol deprivations will increase the reinforcing effects of ethanol within the posterior VTA of P rats. Groups of female P rats were used (alcohol-naive, continuous access, and repeatedly deprived). Each rat was implanted with a guide cannula aimed at the posterior VTA. Depression of the active lever produced the infusion of 100 nl of artificial cerebrospinal fluid (CSF) or ethanol (25-300 mg%). Each rat was given only one ethanol concentration during the 4-h sessions conducted every other day. Compared with the infusions of artificial CSF, the alcohol-naive group reliably self-infused 75 and 150 mg% ethanol, but not the lower or higher concentrations. On the other hand, the continuous access group had significantly higher self-infusions of 50, 75, 150, and 300 mg% ethanol compared with artificial CSF infusions. The repeatedly deprived group also self-infused significantly more of 50, 75, 150, and 300 mg% ethanol than artificial CSF; moreover, the number of infusions for all four concentrations was higher in the repeatedly deprived versus the continuous access group. Chronic alcohol drinking by P rats increased the reinforcing effects of ethanol within the posterior VTA, and repeated alcohol deprivations produced a further increase in these reinforcing effects of ethanol.

Chronic ethanol drinking by alcohol-preferring rats increases the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol.

BACKGROUND: The ventral tegmental area (VTA) is involved in regulating ethanol drinking, and the posterior VTA seems to be a neuroanatomical substrate that mediates the reinforcing effects of ethanol in ethanol-naive Wistar and ethanol-naive alcohol-preferring (P) rats. The objective of this study was to test the hypothesis that chronic ethanol drinking increases the sensitivity of the posterior VTA to the reinforcing effects of ethanol. METHODS: Two groups of female P rats (one given water as its sole source of fluid and the other given 24-hr free-choice access to 15% ethanol and water for at least 8 weeks) were stereotaxically implanted with guide cannulae aimed at the posterior VTA. One week after surgery, rats were placed in standard two-lever (active and inactive) operant chambers and connected to the microinfusion system. Depression of the active lever produced the infusion of 100 nl of artificial cerebrospinal fluid (CSF) or ethanol. The ethanol-naive and chronic ethanol-drinking groups were assigned to subgroups to receive artificial CSF or 25, 50, 75, or 125 mg/dl of ethanol (n = 6-9/dose/group) to self-infuse (FR1 schedule) during the 4-hr sessions given every other day. RESULTS: Compared with the infusions of artificial CSF, the control group reliably (p < 0.05) self-infused 75 and 125 mg/dl of ethanol but not the lower concentrations. The ethanol-drinking group had significantly (p < 0.05) higher self-infusions of 50, 75, and 125 mg/dl of ethanol than artificial CSF during the four acquisition sessions; the number of infusions of all three doses was higher in the ethanol-drinking group than in the ethanol-naive group. Both groups decreased responding on the active lever when artificial CSF was substituted for ethanol, and both groups demonstrated robust reinstatement of responding on the active lever when ethanol was restored. CONCLUSIONS: Chronic ethanol drinking by P rats increased the sensitivity of the posterior VTA to the reinforcing effects of ethanol.