Sedation and the stimulus properties of antihistamines

A group of six rats was trained to discriminate the effects of diphenhydramine (10 mg/kg; 30 min pretreatment time) and saline in a two-lever choice task using a fixed ratio schedule of water reinforcement. Stimulus control was assumed to be present when 80% or more of the first ten responses were appropriate for the treatment condition on each of five consecutive days. Diphenhydramine established stimulus control in each of the subjects. The mean number of sessions prior to the onset of criterion performance was 26 (standard error = 7). A second group of six rats was similarly trained with chlorpheniramine (10 mg/kg; 30 min pretreatment time) and saline. Four of the group reached criterion performance in a mean of 56 sessions (SE = 7). The diphenhydramine stimulus generalized completely to promethazine, azatidine, and chlorpheniramine. In rats trained with chlorpheniramine, only promethazine and azatidine substituted completely while diphenhydramine yielded intermediate results, i.e., significantly different from both training conditions. It is concluded that the relative propensity of antihistamines to induce sedation in humans is not correlated with distinctive stimulus properties in the rat.