Scopolamine produces environment-specific conditioned activity that is not blocked by pimozide in rats.

A classical conditioning paradigm was employed to determine if the stimulant effects of the anticholinergic scopolamine could show conditioning. In experiment 1 rats had 12 60-min pairings of scopolamine (1.0 or 8.0 mg/kg, IP) with a distinctive environment that monitored horizontal and vertical activity. Experimental (paired) groups received the drug 30 min prior to each session, whereas control (unpaired) groups received saline. Following each session the Paired groups were injected with saline, and the Unpaired groups received the same doses of scopolamine. After every fourth pairing a test session assessed conditioning by comparing activity of paired und unpaired groups in response to saline. Scopolamine enhanced horizontal activity, although conditioning was seen only with 8.0 mg/kg. The low dose increased vertical activity, whereas an initial decrease was observed with 8.0 mg/kg. However, conditioned vertical activity was seen with both doses. Experiment 2 assessed the possible role of dopamine in conditioning with 8.0 mg/kg scopolamine. Rats treated as in experiment 1 were additionally given 0.4 mg/kg pimozide 4 h prior to each pairing session. Pimozide did not block scopolamine's stimulant effect. Conditioned horizontal and vertical activity were also observed, suggesting that this effect may be mediated by direct changes within cholinergic systems.