Electrophysiological and biochemical characterization of the development of alpha 1-adrenergic and 5-HT1 receptors associated with dorsal raphe neurons.
Electrophysiological and quantitative autoradiographic receptor binding approaches were used to characterize the postnatal development of alpha 1-adrenergic and serotonergic receptors in the midbrain dorsal raphe nucleus (DRN) in rats. Dose-response data were obtained from extracellular records of the firing of DRN neurons recorded in midbrain slices perfused with artificial cerebral spinal fluid containing varying concentrations of the drugs investigated. These data indicated that DRN neurons, at all postnatal ages, are equally sensitive to the excitatory effects of phenylephrine (an alpha 1-norepinephrine agonist) and the inhibitory effects of serotonin (5-HT). In contrast, LSD (a 5-HT agonist) was considerably more potent in neonates as compared to adults. With one exception, the autoradiographic binding data was found to be in agreement with the electrophysiological findings. There were no observed changes in the number of alpha 1-adrenergic ([3H]prazosin) binding sites at different ages suggesting that cells in this region exhibit functionally mature alpha 1-adrenergic responses at birth. Similarly, the number of [3H]LSD binding sites was found to increase in older animals consistent with the increased potency of LSD in older animals. Paradoxically, the number of [3H]5-HT sites was observed to increase with age, a finding inconsistent with the functional data obtained using 5-HT in the slice. Hypotheses for the observed discrepancy are examined.
Smith
D A
DA
Yale University School of Medicine, Department of Psychiatry, New Haven, CT 06508.
Gallager
D W
DW
D000200:Action Potentials / Q000187:drug effects; D000375:Aging / Q000502:physiology*; D000818:Animals; D066298:In Vitro Techniques; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011903:Raphe Nuclei / Q000254:growth & development / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D010656:Phenylephrine; D012701:Serotonin; D008238:Lysergic Acid Diethylamide