Scopolamine does not restore normal conditioned avoidance performance in raclopride-treated rats

Several studies have shown antagonism by anticholinergics of antipsychotic-induced suppression of conditioned avoidance behavior, as well as of catalepsy, in rats. These observations provide pharmacological evidence for these behaviors mediated via nigro-striatal dopaminergic projections, as well as known dopaminergic-cholinergic interactions in the neostriatum. The objective of the present study was to examine the quality of behavioral change produced by scopolamine (0.25-1.00 mgkg(-1) s.c.) on conditioned avoidance behavior, by itself, and in combination with raclopride (0.1 mgkg(-1) s.c.) in the rat. Adult male Wistar rats were trained to perform a conditioned avoidance response requiring a brightness discrimination. A two-way avoidance shuttle-box was used with the modification that there were two passages in the partition separating the two compartments of the shuttle-box. In order to make a correct avoidance in the response to white noise conditioned stimulus, the rat had to take background light into consideration. Correct passage under dim background conditions was to the left and, with increased background lights, to the right. A weak, intermittent, electric shock (approximately 0.2 mA) was used as unconditioned stimulus. Scopolamine by itself (0.25-1.00 mgkg(-1) s.c.) disrupted the visual discrimination without affecting avoidance performance. As expected, raclopride (0.1 mgkg(-1) s.c.) produced a suppression of conditioned avoidance behavior. A dose of 1.00 mgkg(-1) of scopolamine was needed to restore raclopride-induced suppression of conditioned avoidance behavior. Thus, restoration of the avoidance behavior by scopolamine treatment was not possible at doses that allow normal performance of the visual discrimination. It is concluded that anticholinergics do not restore normal behavior after neuroleptic-induced suppression of conditioned avoidance behavior.