A mixed design was used with the between factor of nor-BNI pretreatment condition (vehicle, nor-BNI 2 h, nor-BNI 24 h) and within factor of Yohimbine condition (vehicle, 2.5 mg/kg, i.p.). During testing, each rat was injected with the nor-BNI vehicle 2 h before, or nor-BNI (10 mg/kg,
i.p.), 2 or 24 h prior to injections of the yohimbine Inhibitors,research,lifescience,medical vehicle (water) or yohimbine. Forty-five minutes after the vehicle or yohimbine injections, rats were placed in the selleck operant chambers for the 1-h reinstatement test session. Experiment 4: Effect of nor-BNI on reinstatement of alcohol seeking by alcohol-associated cues Twenty-two rats (n = 11 per group), trained to self-administer alcohol and their responding extinguished as above, were used to determine the effects of Inhibitors,research,lifescience,medical nor-BNI on reinstatement induced by the light/tone cue previously associated with alcohol self-administration. A mixed design was used with the between factor of nor-BNI pretreatment condition (vehicle, nor-BNI 2 h) and within factor of Cue condition (No cue,
Cue). During testing, each rat was injected with the nor-BNI Inhibitors,research,lifescience,medical vehicle or nor-BNI (10 mg/kg, i.p.) 2 h prior to 1-h test sessions. Rats were placed in the operant chambers and received one non-contingent presentation of the tone-light cue. Subsequent presses on the active lever resulted in cue presentation on a FR1 schedule during the remainder of the session. Extinction responding without cue presentation the previous day was used as the baseline. Inhibitors,research,lifescience,medical A 24 h nor-BNI condition was not included as such pretreatment did not affect U50,488- and yohimbine-induced reinstatement in Experiments 2 and 3. Experiment 5: Effect of antalarmin on U50,488-induced reinstatement of alcohol seeking Twenty-four rats (n = 12 per group)
were trained and their responding was extinguished as above and they were used to assess the effect of antalarmin on U50,488-induced reinstatement. Inhibitors,research,lifescience,medical A mixed design was used with the between factor of U50,488 dose (vehicle, 5 mg/kg, i.p.) and within factor of Antalarmin dose (vehicle, 10, 20 mg/kg, i.p.). On the test days, each rat was injected with the antalarmin vehicle (10% cremophor in saline) or one of the doses of antalarmin, and 30 min later with vehicle or U50,488. Thirty minutes after the vehicle or U50,488 injections, rats were placed in the operant conditioning chambers for a 1-h reinstatement only test session. There were at least 2 days between drug tests, and on these days animals were injected with water, i.p. and received extinction sessions. Results Figure Figure11 shows the mean number of alcohol deliveries (A) and intake in g/kg (B) during alcohol self-administration training of the animals in the experiments. The average numbers of active lever responses (±SEM) made over the last 3 days of alcohol self-administration were 82.78 ± 4.12. Figure 1 Alcohol self-administration.