COMPARATIVE ONTOGENIC PROFILE OF CHOLINERGIC MARKERS, INCLUDING NICOTINIC AND MUSCARINIC RECEPTORS, IN THE RAT-BRAIN

The ontogenic profiles of several cholinergic markers were assessed in the rat brain by using quantitative in vitro receptor autoradiography . Brain sections from animals at different stages of development were processed with [H-3]AH5183 (vesamicol; vesicular acetylcholine transpo rt sites), [H-3]N-methylcarbamylcholine (alpha(4) beta(2) nicotinic re ceptor sites), [H-3]hemicholinium-3 (high-affinity choline uptake site s), [H-3]3-quinuclidinyl benzilate (total population of muscarinic rec eptor sites), [H-3]4-DAMP (muscarinic M(1)/M(3)9 receptor sites), [H-3 ]pirenzepine (muscarinic M(1) receptor sites), and [H-3]AF-DX 116 and [H-3]AF-DX 384 (muscarinic M(2) receptor sites) as radiolabeled probes . The results revealed that, by the end of the prenatal period (embryo nic day 20), the densities of nicotinic receptor and vesicular acetylc holine transport sites already represented a considerable proportion o f those observed in adulthood (postnatal day 60) in different laminae of the frontal, parietal, and occipital cortices, in the layers of Amm on's horn fields and the dentate gyrus of the hippocampal formation, a s well as in the amygdaloid body, the olfactory tubercle, and the stri atum. In contrast, at that stage, the densities of total muscarinic, M (1)/M(3), M(1), and possibly M(2) receptor and high-affinity choline u ptake sites represent only a small proportion of levels seen in the ad ult. Differences were also observed in the postnatal ontogenic profile s of nicotinic, muscarinic, vesamicol, and high-affinity choline uptak e sites. For example, between postnatal weeks 3 and 5, the levels of M (1)/M(3) and M(1) sites were at least as high as in the adult, whereas M(2) and high-affinity choline uptake site densities appeared to be d elayed and to reach adult values only after postnatal week 5. With reg ard to cholinergic innervation in the developing rat brain, the presen t findings suggest a temporal establishment of several components of t he cholinergic systems. The first components are the vesicular acetylc holine transporter and nicotinic sites; these are followed by M(1)/M(3 ) and M(1) sites and, finally, by Mt and high-affinity choline uptake sites. (C) 1996 Wiley-Liss, Inc.