Distribution of ?2A-adrenergic receptor-like immunoreactivity in the rat central nervous system

Talley, Edmund M.; Rosin, Diane L.; Lee, Amy; Guyenet, Patrice G.; Lynch, Kevin R.

doi:10.1002/(sici)1096-9861(19960812)372:1<111::aid-cne8>3.0.co;2-6

Cited by 218 publications

(121 citation statements)

References 36 publications

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“…[ 3 H]RX821002 binding has been reported to recognize the α2A and α2C subtypes of the adrenergic receptor, whereas [ 125 I]-p-iodoclonidine is more selective for the α2A form (Wallace et al, 1994). High levels of the α2A-adrenergic receptor and its mRNA are present in the LC (McCune et al, 1993;Nicholas et al, 1993;Scheinin et al, 1994;Talley et al, 1996), where it functions as an autoreceptor on NE neurons (Norenberg et al, 1997;Callado and Stamford, 1999). Low levels of the α2C subtype are expressed in the LC, yet higher density occurs in other regions including cerebral cortex (McCune et al, 1993;Nicholas et al, 1993;Scheinin et al, 1994;Rosin et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

et al. 2007

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Children exposed to cocaine during gestation have a higher incidence of neurobehavioral deficits. The neurochemical bases of these deficits have not been determined, but the pharmacology of cocaine and the nature of the abnormalities suggest that disruptions in catecholaminergic systems may be involved. In the current study, we used a rat model of prenatal cocaine exposure to examine the impact that this exposure has on the locus coeruleus (LC) noradrenergic system in offspring. Pregnant rats received twice-daily intravenous injections of cocaine (3 mg/kg) or saline between gestational days 10 and 20, and progeny were tested as juveniles. Exposure to a mild stressor elevated an index of norepinephrine turnover in the prefrontal cortex and also increased Fos expression in tyrosine hydroxylase-positive LC neurons in rats exposed to prenatal cocaine but not in rats exposed to prenatal saline. No change in the number of tyrosine hydroxylase-positive neurons in the LC was observed between the two prenatal treatment groups. Specific binding of [ 125 I]-para-iodoclonidine, a radioligand with specificity for high affinity α2A-adrenergic receptors, was decreased in the LC of rats exposed to prenatal cocaine compared to prenatal saline controls. As α 2 -adrenergic receptors on LC norepinephrine neurons function as autoreceptors, their down-regulation by prenatal cocaine exposure provides a plausible mechanism for the observed heightened reactivity of norepinephrine neurons in these animals. These data indicate that prenatal cocaine exposure results in lasting changes to the regulation and responsivity of rat LC norepinephrine neurons. A similar dysregulation of LC norepinephrine neurons may occur in children exposed to cocaine during gestation, and this may explain, at least partly, the increased incidence of cognitive deficits that have been observed in these subjects.

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Section: Discussionmentioning

confidence: 99%

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

et al. 2007

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“…Our results point to the a 2A AR being the prime receptor subtype mediating the suppressant action of dexmedetomidine on discrete cue and contextual fear learning. a 2A ARs are expressed in the amygdala where they are located on both the postsynaptic amygdala neurons or presynaptically on noradrenergic terminals (Talley et al, 1996). Immunocytochemical studies of the rat brainstem have shown that a 2A receptors are found on the axon terminals and dendrites of noradrenergic locus coeruleus neurons that project to the lateral and basolateral amygdala nuclei (Lee et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Activation of α2 Adrenergic Receptors Suppresses Fear Conditioning: Expression of c-Fos and Phosphorylated CREB in Mouse Amygdala

Davies

Tsui

Flannery

et al. 2003

Neuropsychopharmacol

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a 2 adrenergic agonists such as dexmedetomidine generally suppress noradrenergic transmission and have sedative, analgesic, and antihypertensive properties. Considering the importance of the neurotransmitter norepinephrine in forming memories for fearful events, we have investigated the acute and chronic effects of dexmedetomidine on discrete cue and contextual fear conditioning in mice. When administered before training, dexmedetomidine (10-20 mg/kg, i.p.) selectively suppressed discrete cue fear conditioning without affecting contextual memory. This behavioral change was associated with a decrease in memory retrieval-induced expression of c-Fos and P-CREB in the lateral, basolateral, and central nuclei of the amygdala. Dexmedetomidine's action on discrete cue memory did not occur in a 2A adrenoceptor knockout (KO) mice. When dexmedetomidine was administered after training, it suppressed contextual memory, an effect that did not occur in a 2A adrenoceptor KO mice. We conclude that dexmedetomidine, acting at a 2A adrenoceptors, must be present during the encoding process to decrease discrete cue fear memory; however, its ability to suppress contextual memory is likely the result of blocking the consolidation process. The ability of a 2 agonists to suppress fear memory may be a valuable property clinically in order to suppress the formation of memories during stressful situations.

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“…21,25 Briefly, the ␣ 2C -AR gene was inactivated in 129/Sv embryonic stem cells 31 which were injected into C57BL/6J blastocysts, and the resulting chimeric mice were bred to F 1 (C57BL/6J × DBA/2J) animals. These animals were back-crossed for several generations to C57BL/6J mice; then intercrossed, and the tested ␣ 2C -KO mice were offspring of closely related F [11][12] pairs, which were combinations of mice with wild-type, heterozygous or homozygous genotypes for the ␣ 2C -AR mutation. All tested ␣ 2C -KO mice were homozygous for the mutation.…”

Section: Animalsmentioning

confidence: 99%

“…6 The three cloned ␣ 2 -AR subtypes, designated as ␣ 2A , ␣ 2B , and ␣ 2C , are well conserved across species and have distinct tissue and cellular distributions. [7][8][9][10][11][12] All ␣ 2 -AR subtypes couple to inhibitory G-proteins, but also differCorrespondence: Dr J Sallinen, Orion Corporation, Orion Pharma, PO Box 425, FIN-20101 Turku, Finland. E-mail: jukka.sallinen@ orion.fi Received 29 October 1998; revised 7 January and 16 February 1999; accepted 16 February 1999 ences have been demonstrated in their intracellular coupling and trafficking.…”

Section: Introductionmentioning

confidence: 99%

Genetic alteration of the α2-adrenoceptor subtype c in mice affects the development of behavioral despair and stress-induced increases in plasma corticosterone levels

et al. 1999

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␣ 2 -Adrenoceptors (␣ 2 -AR) modulate many central nervous system functions, such as regulation of sympathetic tone, vigilance, attention, and reactivity to environmental stressors. Three ␣ 2 -AR subtypes (␣ 2A , ␣ 2B , and ␣ 2C ) with distinct tissue-distribution patterns are known to exist, but the functional significance of each subtype is not clear. Since specific, ␣ 2 -AR subtype-selective pharmacological probes are not available, mice with genetically altered ␣ 2C -AR expression were studied in order to investigate the possible involvement of the ␣ 2C -AR in physiological and behavioral responses to acute and repeated stress. A modified version of Porsolt's forced swimming test was used to assess the possible effects of altered ␣ 2C -AR expression on the development of behavioral despair. ␣ 2C -Overexpression increased and the lack of ␣ 2C -AR (␣ 2C -KO) decreased the immobility of mice in the forced swimming test, ie ␣ 2C -AR expression appeared to promote the development of behavioral despair. In addition, ␣ 2C -KO was associated with attenuated elevation of plasma corticosterone after different stressors, and overexpression of ␣ 2C -ARs was linked with increased corticosterone levels after repeated stress. Moreover, the brain dopamine and serotonin balance, but not norepinephrine turnover, was dependent on ␣ 2C -AR expression, and the expression of c-fos and junB mRNA was increased in ␣ 2C -KO mice. Since ␣ 2C -KO produced stress-protective effects, and ␣ 2C -AR overexpression seemed to promote the development of changes related to depression, it is suggested that a yet-to-be developed subtype-selective ␣ 2C -AR antagonist might have therapeutic value in the treatment of stress-related neuropsychiatric disorders.

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Distribution of ?2A-adrenergic receptor-like immunoreactivity in the rat central nervous system

Cited by 218 publications

References 36 publications

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

Activation of α2 Adrenergic Receptors Suppresses Fear Conditioning: Expression of c-Fos and Phosphorylated CREB in Mouse Amygdala

Genetic alteration of the α2-adrenoceptor subtype c in mice affects the development of behavioral despair and stress-induced increases in plasma corticosterone levels

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