NICOTINIC, MUSCARINIC AND DOPAMINERGIC ACTIONS IN THE VENTRAL HIPPOCAMPUS AND THE NUCLEUS-ACCUMBENS - EFFECTS ON SPATIAL WORKING-MEMORY IN RATS

Acetylcholine (ACh) systems have been widely shown to be important for memory. In particular, ACh hippocampal neurons are critical for memor y formation, though ACh innervation of other areas such as the nucleus accumbens may also be important. There has also been increasing inter est in ACh and dopaminergic (DA) interactions with regard to short-ter m spatial memory. In a series of studies, we have found that ACh and D A agonists and antagonists given systemically interact to influence me mory. The critical neural loci of these interactions are not currently known. In the present study, we used local infusion techniques to exa mine the role of ACh and DA transmitter systems in the nucleus accumbe ns and the ventral hippocampus on radial-arm maze (RAM) working memory performance. Into the nucleus accumbens of rats, we infused the nicot inic ACh agonist nicotine, the nicotinic ACh antagonist mecamylamine, the DA agonist apomorphine, or the DA antagonist haloperidol. Into the ventral hippocampus, we infused nicotine, mecamylamine, the muscarini c ACh agonist pilocarpine, or the muscarinic ACh antagonist, scopolami ne. The nicotinic ACh and DA interaction was tested by a hippocampal i nfusion of mecamylamine alone or together with the DA D-2 agonist quin pirole given via subcutaneous injection. The results confirmed that bo th nicotinic and muscarinic ACh receptors in the ventral hippocampus p lay a significant role in spatial working memory. Blockade of either n icotinic or muscarinic ACh receptors caused significant impairments in RAM choice accuracy. However, infusion of either nicotinic or muscari nic agonists failed to improve choice accuracy. The interaction of DA D-2 systems is different with hippocampal nicotinic blockade than with general nicotinic blockade. Systemic administration of quinpirole pot entiated the amnestic effect of mecamylamine infused into the ventral hippocampus, whereas it was previously found to reverse the amnestic e ffect of systemically administered mecamylamine. In contrast to the si gnificant effects of mecamylamine in the hippocampus, no effects were found after infusion into the nucleus accumbens. Nicotine also was not found to have a significant effect bn memory after intra-accumbens in fusion. Neither the DA agonist apomorphine nor the DA antagonist halop eridol had a significant effect on memory after infusion into the nucl eus accumbens. This study provides support for the involvement of nico tinic and muscarinic receptors in the ventral hippocampus in memory fu nction. Ventral hippocampal nicotinic systems have significant interac tions with D-2 systems, but these differ from their systemic interacti ons. In contrast, nicotinic ACh and DA systems in the nucleus accumben s were not found in the current study to be important for working memo ry performance in the RAM.