Place learning and object recognition by rats subjected to transection of the fimbria-fornix and/or ablation of the prefrontal cortex.

The acquisition of a water maze-based allocentric place learning task and an exploration based object recognition task were studied in four groups of rats: animals in which the fimbria-fornix had been transected, rats who had received bilateral ablations of the anteromedial prefrontal cortex, animals in which both of these structures had been lesioned, and a sham operated control group. None of the groups showed impairments of object recognition. Ablations of the prefrontal cortex caused a mild impairment in the acquisition of the place learning task. The two fimbria-fornix transected groups exhibited a severe impairment during the acquisition of this task. All groups reached criterion level task performance eventually. All groups were subjected to a number of behavioural and pharmacological challenges in order to elucidate the neural and cognitive mechanisms of this behavioural recovery. During a no-platform session both the fimbria-fornix transected group and the prefrontally ablated group demonstrated a normal preference for the former platform position. The combined lesion group, however, failed to show a similar preference for this position. The outcome of the pharmacological challenges demonstrated that while the task performance of all four groups relied equally on catecholaminergic mediation, only the task solution of the fimbria-fornix transected group was significantly impaired by disturbance of the catecholaminergic systems. The data indicated a high likelihood that prefrontal cortical mechanisms contribute to the recovery of allocentric place learning after fimbria-fornix transections.

Associative and nonassociative learning after chronic imipramine in rats.

We investigated effects of 15 daily injections of imipramine (20 mg/kg; in one experiment also 10 and 30 mg/kg). The associative learning types (place learning and object recognition) as well as nonassociative learning (habituation of exploration in an open field and within the object recognition test) were studied. Tests were performed immediately after the final injection (early test) and 24 h after the final injection (late test). The 5-HT(1A), 5-HT(1B/D), 5-HT(2A), beta-adrenergic, D(2) receptors were assayed 24 h after the final injection and the 5-HT(2A) and beta-adrenergic receptors were also measured 60 and 96 h after the final injection. While associative types of learning were impaired in early tests, they remained unaffected in late tests and, while the nonassociative learning (habituation of exploration) remained unaffected in early tests, it was changed in late tests. Measured 24 h after the final injection, imipramine (20 and 30 mg/kg per day) down-regulated the concentration of beta-adrenergic and 5-HT(2A) receptors, while leaving all other measured receptors unaffected. However, only the down-regulation of the 5-HT(2A) receptor outlasted the initial 24-h period after the final injection. On the basis of present and previous results, we interpret the impairment of associative types of learning in early tests as a reflection of anticholinergic effects of imipramine, while the modifications of habituation of exploration in late tests are likely primarily to be mediated by imipramine-provoked regulations of serotonergic receptors.