Simultaneous modulation of hippocampal cholinergic activity and extinction by intraseptal muscimol.

The relationship between regulation of acetylcholine metabolism in the septal-hippocampal pathway and extinction of a food reinforced lever press response was investigated by comparing the turnover rate of acetylcholine (TRACh) in the rat hippocampus with the amount of responding during extinction after intraseptal injection of the gamma-aminobutyric acid receptor agonist muscimol. Doses (0.3-3.0 nmol) which decreased the TRACh in the hippocampus also increased the responding during extinction over that of saline controls. Responding during the continuous reinforcement schedule before extinction was also increased, but to a lesser extent. Higher doses (10-30 nmol) further decreased the TRACh in the hippocampus, decreased it in the cortex and were accompanied by irregular responding and sedation. The TRACh in the hippocampus was also measured in drug-free rats undergoing extinction after training on a continuous reinforcement or variable interval 60 sec reinforcement schedule. Although the variable interval 60 sec reinforcement schedule rats responded more than the continuous reinforcement rats during extinction, there were no differences between the TRACh in the hippocampus. The present results indicate that the decrease in the hippocampal TRACh which is produced by intraseptal muscimol is accompanied by an increase in the response rate during extinction, but that operantly induced differences in this behavior are not accompanied by detectable changes in hippocampal TRACh.