Interaction of cholinergic-dopaminergic systems in the regulation of memory storage in aversively motivated learning tasks

Abstract

These experiments examined the interaction between muscarinic cholinergic 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 dose-response effects, on retention, of agonists and antagonists specific for either D 1- or D 2-receptors. Immediately posttraining mice were given i.p. injections of saline, the D 1-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 D 1-receptor antagonists SCH 23390 (0.03 (0.03, 0.1, 0.3 or 1.0 mg/kg), the D 2-receptor agonist quinpirole (0.3, 1.0 or 3.0 mg/kg) or the D 2-receptor antagonist sulpiride (3.0, 10.0, 30.0 or 100.0 mg/kg). Retention was tested 48 h later. The drugs affecting D 1-receptors did not affect retention. In contrast, in both tasks quinpirole enhanced retention and sulpiride impaired retention. In the IA task, quinpirole (3.0 mg/kg) blocked the retention impairing effects of the muscarinic cholinergic antagonist 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 muscarinic cholinergic agonist oxotremorine (35.0 or 70.0 μg/kg). D 1-receptor agents did not modify the effects of either atropine or oxotremorine on retention of the IA response. These findings suggest that the effects of cholinergic muscarinic agents on retention of the IA response are mediated by influences involving D 2-dopaminergic mechanisms. In the YMD task, atropine (10.0 mg/kg) blocked the memory-enhancing effects of quinpirole (3.0 mg/kg) and oxotremorine (35.0 or 70.0 μg/kg) attenuated the memory impairing effect of sulpiride (3.0, 10.0, 30.0 or 100.0 mg/kg). D 1-receptor agents did not modify the effects of either atropine or oxotremorine on retention of the YMD task. These results suggest that the effects of the D 2-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 between D 2-dopaminergic and muscarinic cholinergic systems, the ways in which these mechanisms interact are task-dependent.