Evaluation of the discriminative stimulus effects of venlafaxine, a potential antidepressant, in rhesus monkeys

Abstract

AbstractThe discriminative stimulus effects of the novel antidepressant venlafaxine were examined in rhesus monkeys. Separate groups of monkeys discriminated either 0.56 or 1.0 mg/kg (i.g.) d‐amphetamine (N = 3) or 10 mg/kg (i.g.) pentobarbital (N = 4) from saline, in a discrete‐trials shock avoidance/escape paradigm. In d‐amphetamine‐trained monkeys, 10–17 mg/kg venlafaxine occasioned only saline‐appropriate responding and had minimal effect on response latency in alll monkeys. The highest dose of venlafaxine tested (30 mg/kg) occasioned at least 95% d‐amphetamine‐lever responding in two of three monkeys. Following this dose, the average latency to respond after the onset of a trial increased substantially in both monkeys; in one monkey avoidance responding was disrupted and shocks were occasionally received. In the third monkey, 30 mg/kg venlafaxine occasioned only saline‐lever responding and had no effect on response latency. In pentobarbital‐trained monkeys, venlafaxine (3.0–30 mg/kg) occasioned primarily saline‐lever responding and these doses had minimal effects on response latency. In general, venlafaxine was more potent in d‐amphetamine‐trained monkeys than in pentobarbital‐trained monkeys in its effects on response latency. Drug discrimination procedures in animals have been shown to differentiate compunds in a manner that is consistent with their subjective effects. Thus, result from the present experiment suggest that venlafaxine may produce subjective effects similar to d‐amphetamine in some individuals, but only at high doses.