INTERACTION OF CHOLINERGIC-DOPAMINERGIC SYSTEMS IN THE REGULATION OF MEMORY STORAGE IN AVERSIVELY MOTIVATED LEARNING-TASKS

These experiments examined the interaction between muscarinic choliner gic and dopaminergic systems in the modulation of memory storage. Male CD1 mice (25-30 g) were trained in an inhibitory avoidance (IA) and a Y-maze discrimination (YMD) task. The first experiment examined the d ose-response effects, on retention. of agonists and antagonists specif ic for either D1- or D2-receptors. Immediately posttraining mice were given i.p. injections of saline, the D2-receptor agonists SKF 38393 (3 .0, 10.0 or 30.0 mg/kg) or SKF 77434 (3.0, 10.0 or 30.0 mg/kg), the D1 -receptor antagonist SCH 23390 (0.03, 0.1. 0.3 or 1.0 mg/kg), the D2-r eceptor agonist quinpirole (0.3, 1.0 or 3.0 mg/kg) or the D2-receptor antagonist sulpiride (3.0, 10.0, 30.0 or 100.0 mg/kg). Retention was t ested 48 h later. The drugs affecting D1-receptors did not affect rete ntion. In contrast, in both tasks quinpirole enhanced retention and su lpiride impaired retention. In the IA task, quinpirole (3.0 mg/kg) blo cked the retention impairing effects of the muscarinic cholinergic ant agonist atropine (10.0 mg/kg), and sulpiride (3.0, 10.0, 30.0 or 100.0 mg/kg) significantly attenuated the memory enhancing effects of the m uscarinic cholinergic agonist oxotremorine (35.0 or 70.0 mug/kg). D1-r eceptor agents did not modify the effects of either atropine or oxotre morine on retention of the IA response. These findings suggest that th e effects of cholinergic muscarinic agents on retention of the IA resp onse are mediated by influences involving D2-dopaminergic mechanisms. In the YMD task, atropine (10.0 mg/kg) blocked the memory-enhancing ef fects of quinpirole (3.0 mg/kg) and oxotremorine (35.0 or 70.0 mug/kg) attenuated the memory impairing effect of sulpiride (3.0, 10.0, 30.0 or 100.0 mg/kg). D,-receptor agents did not modify the effects of eith er atropine or oxotremorine on retention of the YMD task. These result s suggest that the effects of the D2-dopaminergic agents on retention of the YMD are mediated by muscarinic cholinergic mechanisms. Although retention of both the IA and the YMD are modulated by interactions be tween D2-dopaminergic and muscarinic cholinergic systems, the ways in which these mechanisms interact are task-dependent.