MUSCARINIC RECEPTOR CHARACTERISTICS AND REGULATION IN RAT CEREBRAL-CORTEX - CHANGES DURING DEVELOPMENT, AGING AND THE ESTROUS-CYCLE

The effects of postnatal development, aging and the oestrous cycle on muscarinic acetylcholine receptor (mAChR) properties were examined in in vitro living slices of rat neocortex. Using the hydrophilic antagon ist ([H-3]NMS) to label cell surface mAChRs, an increase in both B-max and K-d was found during the first postnatal weeks. These values peak ed at between 20 - 40 days postnatally and then declined to adult leve ls. After 3 months of age, a steady decline in receptor number started : it was 10.1% lower at 10 months and 38.7% lower at 17 months of age. In contrast, K-d values increased, being 31.7 and 20% higher respecti vely at these ages. Carbachol-induced (4 h at 37 degrees C) down-regul ation of receptor number was similar to 22.2% in newborn and 26.1% in adult (3-month-old) rats, but only 16.3% at 20 - 40 days of age. The d egree of carbachol-induced down-regulation of mAChR was not affected i n the older animals. Veratridine, which increases neural activity, als o induced a significant reduction in [H-3]NMS binding sites of 11.4% i n rats aged 0-20 days and 22.4% in 3-month-old rats, but at 20 - 40 an d 40 - 60 days of age no significant down-regulation of receptor numbe r was observed. Furthermore, down-regulation was absent in the 10-mont h-old rats as well. Since a great variation in B-max and K-d values wa s seen in 3-month-old females but not in male rats, we investigated mA ChR characteristics during the oestrous cycle of female rats. In pro-o estrus, mACh receptor number was increased and affinity decreased in c omparison with di-oestrus; The transition from pro-oestrus into oestru s was accompanied by a significant decrease in receptor number and an increase in receptor affinity. Injection of ovariectomized females wit h oestradiol and progesterone induced an increase in the number of bin ding sites and a decrease in affinity. These values are comparable to those seen in pro-oestrous rats. These results demonstrate (i) that bo th carbachol- and veratridine-induced down-regulation of the mACh rece ptor is limited during the critical period of cortical plasticity, (ii ) that after 3 months of age mACh receptor number is gradually declini ng, and (iii) that the steroid hormones oestrogen and progesterone are capable of modifying the characteristics of muscarinic antagonist bin ding sites in the female rat cerebral cortex.