Evaluation of limited and unlimited food intake during withdrawal in triazolam-dependent baboons.

Chronic administration of benzodiazepine (BZ) agonists in baboons typically increases food intake, in a dose-dependent manner, during drug administration and suppresses food intake after termination of drug dosing. To determine if suppressed food intake after termination of chronic BZ administration (i.e. withdrawal) was related to increased food consumption during drug administration, the effects of chronic triazolam (1.0 mg/kg/day, intragastrically, for 30-34 days) and subsequent triazolam withdrawal on food intake was studied under two conditions in each of four baboons: (1) when the number of pellets was unlimited; and (2) when the number of pellets was limited so that pellet intake could not increase above the mean number of pellets per day obtained during a preceding vehicle condition. Pellets were available during daily 20-h sessions under a fixed-ratio 10 schedule of reinforcement. All baboons completed both pellet conditions, and the order of exposure was counterbalanced across subjects. During the unlimited pellet condition, pellets per day were increased during triazolam administration and then were suppressed in a time-limited manner when triazolam was discontinued in all four baboons. When pellet intake was limited during triazolam administration, pellet intake after triazolam discontinuation was suppressed in three of four baboons, and the magnitude and duration of suppression was generally less than during the unlimited pellet condition. Other behavioral signs of withdrawal (e.g., tremor/jerk, vomit/retch) were observed in all four baboons under both pellet conditions. These data suggest that the hyperphagic effects of triazolam appear to contribute to the subsequent suppression of food intake during triazolam withdrawal. However, these hyperphagic effects do not account for the entire phenomenon of suppressed food intake during BZ withdrawal.