Brain amines and effects of chlordiazepoxide on motor activity in response to stress.

The effect of chlordiazepoxide (CDP) on emotional responsiveness to stress was determined in CD-1 male mice. The relationship of the monoamines to the mediation of emotional behavior was examined with drugs having selective actions on serotonin (5-HT), norepinephrine (NE), and dopamine (DA). Emotional behavior as measured by locomotor activity was increased by stress. This activation enhanced the stimulatory effect of low doses of CDP (5 and 10 mg/kg) and attenuated the depressant action of higher doses (20 and 40 mg/kg). Quipazine (0.5 mg/kg) reduced the depressant effect of CDP in stressed animals. Its action failed to support a proposed anti-serotonergic action of CDP and implicated possible dopaminergic involvement. In stressed mice, apomorphine (0.5 mg/kg) and clonidine (0.1 mg/kg) antagonized the stimulatory action of low doses of CDP. Behavioral effects of clonidine provide support for the notion that the stimulatory effects of CDP may be due to enhanced catecholamine (CA) neurotransmission. Whole brain levels of NE and DA were significantly increased when clonidine was combined with CDP. This indicated a possible reduction in CA turnover and activity.