Systemic kainic acid administration to prepubescent rats, in a convulsant dose, results in permanent changes in behaviour, learning and memory in adulthood (Holmes et al., 1988, Epilepsia 29, 721-730). With regard to the hypothesis that cholinergic mechanisms play a crucial role in cognitive processes, M1- and M2-muscarinic acetylcholine receptors, choline acetyltransferase, and high-affinity choline uptake as well as benzodiazepine receptors were studied in selected cortical regions (frontal, temporal, somatosensory, visual, piriform cortex), in amygdala, hippocampus, and in the nucleus basalis of Meynert from adult rats, which received at the age of 25 days a single dosage of 11 mg/kg, s.c. kainic acid. Kainic acid treatment of prepubescent rats resulted in the adult brain in decreased numbers of the total population of muscarinic acetylcholine receptors in frontal (by 27%, P < 0.05, two-tailed Student's t-test), temporal (22%, P < 0.05), and piriform cortex (31%, P < 0.05), in amygdala (24%, P < 0.05), and nucleus basalis of Meynert (39%, P < 0.02). The binding affinity was unchanged in these regions. However, in the hippocampus, the dissociation constant was significantly increased following kainic acid treatment, while the receptor numbers remained unchanged. Analysis of competition experiments with the muscarinic antagonist pirenzepine revealed that the reductions of muscarinic acetylcholine receptors in the cortical regions after kainic acid treatment are mainly due to decreases in the number of the muscarinic M1-receptor subtype. In the amygdala, the numbers of both M1- and M2-receptor subtypes are reduced. In contrast, in the nucleus basalis of Meynert, only the number of the M2-receptor subtype was decreased as a consequence of early kainic acid treatment. In the hippocampus, however, the changes in muscarinic receptor binding are obviously due to an increase in the dissociation constant of the M1-receptor subtype. Early kainic acid treatment resulted in an increased high-affinity choline uptake in the temporal cortex (by 59%, P < 0.05) and in a decreased uptake in the piriform cortex (55%, P < 0.01) as compared to controls. Early kainic acid treatment did not affect the activity of choline acetyltransferase in any of the regions tested. Kainic acid injection to prepubescent rats led in the adult brain to an increase in benzodiazepine receptor binding in the temporal cortex by 51% (P < 0.001). The data suggest that the changes in learning and memory in adult rats after kainic acid injection to prepubescent rats might be related to alterations in cholinergic mechanisms in some regions of the cerebral cortex and limbic system.
