Strain-dependent involvement of D1 and D2 dopamine receptors in muscariniccholinergic influences on memory storage

These experiments examined the interaction of muscarinic and dopaminergic s ystems in influencing memory for one-trial inhibitory avoidance training in mice of the C57BL/6 and DBA/2 strains. In both strains, immediate post-tra ining systemic administration of the muscarinic cholinergic agonist oxotrem orine enhanced retention and the cholinergic antagonist atropine impaired r etention. No effects were seen with injections 2 h post-training. Furthermo re, the drugs did not affect retention performance of animals that received no footshock on the training trial. These results confirm previous finding s indicating that muscarinic cholinergic drugs affect memory by influencing memory consolidation. In C57 mice, pretreatment with selective D1 or D2 do pamine (DA) receptor agonists (SKF 38393 or LY 171555, respectively) in oth erwise non-effective doses (5 and 0.25 mg/kg, respectively) potentiated the effects of oxotremorine (0.04 mg/kg). Furthermore, in C57 mice pretreatmen t with selective D1 or D2 receptor antagonists (SCH 23390 or (-)-sulpiride) in otherwise non-effective doses (0.025 and 6 mg/kg, respectively) blocked the memory enhancing effects of oxotremorine. The memory impairing effects of atropine (3 mg/kg) were blocked by the D1 and D2 selective agonists and potentiated by the selective DI or D2 antagonists. In contrast, in DBA mic e, the D1 and D2 selective agonists antagonised the memory enhancing effect s of oxotremorine (0.02 mg/kg) and potentiated the effects of atropine (2 m g/kg). Furthermore, the D1 and D2 antagonists potentiated the effects of ox otremorine and antagonised those of atropine. These findings indicate that although muscarinic cholinergic influences on memory storage are comparable in mice of these two strains, the cholinergic-dopaminergic interactions ar e opposite in the two strains. These results have implications for hypothes es of cholinergic and dopaminergic regulation of memory storage. (C) 1999 E lsevier Science B.V. All rights reserved.