Peripheral 8-OH-DPAT and scopolamine infused into the frontal cortex produce passive avoidance retention impairments in rats

The present study determined whether peripheral injections of the 5HT_1A agonist (8-OH-DPAT), scopolamine infusions into the frontal cortex, or a combination of both drug treatments would produce impairments in rats trained on passive avoidance. Using a 2×2 design, rats were infused with either bacteriostatic water or 30μg/1μl of scopolamine HCl into the frontal cortex 30min before being trained on passive avoidance. This was followed by injections (ip) of either 0.1% ascorbic acid/bacteriostatic water or 30μg/kg of 8-OH-DPAT 15min later. All subjects were tested for retention 72h later. At test, the initial latency to enter into the black shocked compartment and the total time spent in the white safe compartment (TTW) were recorded. Analysis of the latency data indicated that scopolamine and 8-OH-DPAT, when administered singly or in combination, produced amnesia for the task. Assessment of TTW scores, however, revealed that of the three drug-treated groups, only animals treated with 8-OH-DPAT alone tended to avoid the previously shocked black compartment and spend more time in the white safe compartment. These data indicate that either stimulating 5-HT_1A or blocking frontal cortical muscarinic receptors at training impairs passive avoidance performance and that the deficit following the latter treatment is somewhat more extensive. Implications for the role frontal cortical muscarinic and 5HT_1A receptors play in learning and memory are discussed.