Expression of alpha 2 adrenoceptors during rat brain development--I. Alpha 2A messenger RNA expression.
ABSTRACT The distribution of alpha 2A adrenoceptor messenger RNA expression in developing rat brain was characterized using in situ hybridization with 35S-labeled riboprobes. Intense hybridization signal was detected as early as embryonic day 14 in several areas adjacent to the forebrain and hindbrain germinal zones and in central noradrenergic neurons. A marked increase in messenger RNA expression was observed throughout the brain during late prenatal development, consistent with the migration and maturation of neurons in developing brain structures. In embryonic brain, there was a temporal and spatial correspondence in the appearance of alpha 2A messenger RNA expression and binding sites labeled with [3H]idazoxan or p-[125I]iodoclonidine, indicating translation into receptor protein at an early stage of development. Whereas the presynaptic expression remained constant throughout development, there was an early postnatal decline of alpha 2A receptor expression in many brain regions, including the olfactory bulb, cortex, caudate-putamen, hippocampus, thalamus, hypothalamus and medulla. Thereafter, messenger RNA expression increased, establishing an adult-like pattern during the second postnatal week, but remained low in areas such as the caudate-putamen, thalamus and hippocampus, which do not exhibit extensive expression in the adult. The transient perinatal expression of this alpha 2 adrenoceptor type, which coincides with a period of hyperreactivity to sensory stimuli in the locus coeruleus, may indicate a specific functional role for the alpha 2A receptor in the developing rat brain. The early and intense expression in olfactory structures suggests an involvement in early olfactory learning. The pattern of widespread, transient expression of alpha 2A receptors in the fetal brain is in marked contrast to the postnatal development of the alpha 2C receptor type.
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ABSTRACT: The specific binding of the α2-adrenoceptor antagonists [3H]yohimbine and [3H]rauwolscine to membranes prepared from rat cerebral cortex and human platelets was rapid, reversible, saturable and of high affinity. Both ligands labelled an identical population of sites in cerebral or platelet membranes though the affinities of both agents were significantly lower in brain. The specific binding of [3H]yohimbine and [3H]rauwolscine in both tissues was displaced by various adrenergic agents in a manner that suggests that the labelled sites probably represent the α2-adrenoceptor. There were, however, significant differences in the affinities of certain α-antagonists between cerebral and platelet preparations, even though these agents generated displacement curves with slopes close to unity in both tissues. Thus, whereas yohimbine, rauwolscine, WB4101 and corynanthine were all weaker in cerebral cortex, prazosin was significantly more potent at cortical than in platelet membranes. A possible heterogeneity of α2-adrenoceptors is discussed.European Journal of Pharmacology 11/1982; · 2.59 Impact Factor
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ABSTRACT: Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. Training consisted of 18 trials with an intertrial interval of 24 hr. For the experimental group, a trial consisted of a pairing of unconditioned stimulus (UCS, stroking/tactile stimulation) and the conditioned stimulus (CS, odor). Control groups received either only the CS (Odor only) or only the UCS (Stroke only). Within each training condition, pups were injected with either the NE beta-receptor agonist isoproterenol (1, 20, or 4 mg/kg), the NE beta-receptor antagonist propranolol (10, 20, 40 mg/kg), or saline 30 min prior to training. On day 20, pups received one of the following tests: (1) behavioral conditioned responding, (2) injection with 14C-2-deoxyglucose (2-DG) and exposed to the CS odor, or (3) tested for olfactory bulb mitral/tufted cell single-unit responses to the CS odor. The results indicated that training with either: (1) Odor-Stroke-Saline, (2) Odor-Stroke-Isoproterenol-Propranolol, or (3) Odor only-Isoproterenol (2 mg/kg) was sufficient to produce a learned behavioral odor preference, enhanced uptake of 14C-2-DG in the odor-specific foci within the bulb, and a modified output signal from the bulb as measured by single-cell recordings of mitral/tufted cells. Moreover, propranolol injected prior to Odor-Stroke training blocked the acquisition of both the learned behavior and olfactory bulb responses. Thus, NE is sufficient and may be necessary for the acquisition of both learned olfactory behavior and olfactory bulb responses.Journal of Neuroscience 12/1989; 9(11):3998-4006. · 6.91 Impact Factor
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ABSTRACT: Multiple subtypes of alpha adrenergic receptors with CNS expression (alpha 1A, alpha 1B, alpha 2A and alpha 2C) have been identified through pharmacological and molecular biological means. To characterize the localization of these subtypes and attempt to correlate subtype expression with physiological significance, the expression of the mRNAs encoding the alpha 1A, alpha 1B, alpha 2A and alpha 2C adrenergic receptor subtypes was examined in the adult rat brain by in situ hybridization histochemistry. Each subtype demonstrated a unique pattern of distribution, with the alpha 1 adrenergic receptors more restricted in their distribution and the alpha 2 receptors more widespread. The alpha 1A was primarily localized in the olfactory bulb, intermediate layers of the cortex, the hippocampus and the reticular nucleus of the thalamus. The alpha 1B was expressed in intermediate and deep layers of the cortex, thalamus, hippocampus, dorsal raphe and cerebellum. Although the alpha 2A message was relatively low in abundance, it was identified in the olfactory bulb, cortex, hippocampus, locus coeruleus, pons and cerebellum. The alpha 2C messenger RNA was localized in the cortex (particularly cingulate), hippocampus, caudoputamen, pons and cerebellum. Multiple alpha adrenergic receptor subtypes have significant sequence homology and similar pharmacologic properties; however, they each possess a unique pattern of messenger RNA distribution throughout the brain. The multiplicity of subtypes of alpha adrenergic receptors in specific brain regions may dictate the physiological and pharmacological responses to catecholamines.Neuroscience 12/1993; 57(1):143-51. · 3.12 Impact Factor