The combined effects of chronic ethanol/desipramine treatment on β-adrenoceptor density and coupling efficiency in rat brain

Gurguis, George N.M.; Turkka, Jukka; Karanian, John W.; Linnoila, Markku

doi:10.1016/s0014-2999(98)00810-3

Cited by 4 publications

(3 citation statements)

References 75 publications

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“…This receptor subtype increases intracellular cAMP levels through Gs-alpha activation, but also stimulates the mitogen-activated protein kinase (MAPK) cascade. Chronic ethanol exposure uncouples the ␤ 2 receptor from its G-protein in the frontal cortex of both rats and humans (38,39); the up-regulation found in our study could therefore represent a compensatory mechanism. We also found an up-regulation of frontocortical monoamine oxidase (MAO) A, which preferentially degrades norepinephrine and serotonin.…”

Section: Genes Associated With Neurotransmissionmentioning

confidence: 58%

Long‐lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol

et al. 2002

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Prolonged exposure of the brain to ethanol is a prerequisite for developing ethanol dependence, but the underlying neural adaptations are unknown. Here we demonstrate that rats subjected to repeated cycles of intoxication and withdrawal develop a marked and long-lasting increase in voluntary ethanol intake. Exposure-induced but not spontaneous alcohol intake is antagonized by acamprosate, a compound clinically effective in human alcoholism. Expression analysis of cingulate cortex and amygdala reveals a set of long-term up-regulated transcripts in this model. These include members of pathways previously implicated in alcohol dependence (glutamatergic, endocannabinoid, and monoaminergic neurotransmission), as well as pathways not previously thought to be involved in this disorder (e.g., members of the mitogen-activated protein kinase pathway). Thus, alternating periods of ethanol intoxication and withdrawal are sufficient to induce an altered functional brain state, which is likely to be encoded by long-term changes in gene expression. These observations may have important implications for how alcoholism is managed clinically. Novel clinically effective treatments may be possible to develop by targeting the products of genes found to be regulated in our model.

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Section: Genes Associated With Neurotransmissionmentioning

confidence: 58%

Long‐lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol

et al. 2002

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“…However, chronic ethanol exposure has also been reported to uncouple the β ‐2 adrenergic receptor from its G‐protein in the frontal cortex of both rats and humans (Gurguis et al. , ). Interestingly, while the sensitivity of β ‐adrenergic receptors increases in proportion to anxiety levels in a normal population (Kang and Yu ), β ‐adrenergic receptor sensitivity is lower among individuals under chronic stress (Dimsdale et al.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, there is evidence of increased b-adrenergic receptor sensitivity in the alcohol withdrawal state in rats (Banerjee et al 1978), and b2-adrenoreceptor expression is reportedly upregulated in rats with a history of ethanol self-administration (Rimondini et al 2002). However, chronic ethanol exposure has also been reported to uncouple the b-2 adrenergic receptor from its G-protein in the frontal cortex of both rats and humans (Gurguis et al 1998(Gurguis et al , 1999. Interestingly, while the sensitivity of b-adrenergic receptors increases in proportion to anxiety levels in a normal population (Kang and Yu 2005), b-adrenergic receptor sensitivity is lower among individuals under chronic stress (Dimsdale et al 1994) or suffering from clinical anxiety disorders (Brown et al 1988).…”

Section: Discussionmentioning

confidence: 99%

Chronic treatment with prazosin or duloxetine lessens concurrent anxiety‐like behavior and alcohol intake: evidence of disrupted noradrenergic signaling in anxiety‐related alcohol use

Skelly

Weiner

2014

Brain and Behavior

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BackgroundAlcohol use disorders have been linked to increased anxiety, and enhanced central noradrenergic signaling may partly explain this relationship. Pharmacological interventions believed to reduce the excitatory effects of norepinephrine have proven effective in attenuating ethanol intake in alcoholics as well as in rodent models of ethanol dependence. However, most preclinical investigations into the effectiveness of these drugs in decreasing ethanol intake have been limited to acute observations, and none have concurrently assessed their anxiolytic effects. The purpose of these studies was to examine the long-term effectiveness of pharmacological interventions presumed to decrease norepinephrine signaling on concomitant ethanol self-administration and anxiety-like behavior in adult rats with relatively high levels of antecedent anxiety-like behavior.MethodsAdult male Long-Evans rats self-administered ethanol on an intermittent access schedule for eight to ten weeks prior to being implanted with osmotic minipumps containing either an a1-adrenoreceptor antagonist (prazosin, 1.5 mg/kg/day), a β1/2-adrenoreceptor antagonist (propranolol, 2.5 mg/kg/day), a serotonin/norepinephrine reuptake inhibitor (duloxetine, 1.5 mg/kg/day) or vehicle (10% dimethyl sulfoxide). These drugs were continuously delivered across four weeks, during which animals continued to have intermittent access to ethanol. Anxiety-like behavior was assessed on the elevated plus maze before treatment and again near the end of the drug delivery period.ResultsOur results indicate that chronic treatment with a low dose of prazosin or duloxetine significantly decreases ethanol self-administration (P < 0.05). Furthermore, this decrease in drinking is accompanied by significant reductions in the expression of anxiety-like behavior (P < 0.05).ConclusionsThese findings suggest that chronic treatment with putative inhibitors of central noradrenergic signaling may attenuate ethanol intake via a reduction in anxiety-like behavior.

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Neutrophil β2-adrenoceptor function in major depression: Gs coupling, effects of imipramine and relationship to treatment outcome

Gurguis

Griffith

et al. 1999

European Journal of Pharmacology

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The combined effects of chronic ethanol/desipramine treatment on β-adrenoceptor density and coupling efficiency in rat brain

Cited by 4 publications

References 75 publications

Long‐lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol

Long‐lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol

Chronic treatment with prazosin or duloxetine lessens concurrent anxiety‐like behavior and alcohol intake: evidence of disrupted noradrenergic signaling in anxiety‐related alcohol use

Neutrophil β2-adrenoceptor function in major depression: Gs coupling, effects of imipramine and relationship to treatment outcome

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