Pairing mild stress with increased serotonin‐1B receptor expression in the nucleus accumbens increases susceptibility to amphetamine

Ferguson, Susan M.; Sandygren, N.A.; Neumaier, John F.

doi:10.1111/j.1460-9568.2009.06933.x

Cited by 16 publications

(19 citation statements)

References 38 publications

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“…Following USS the number of Type IIB neurons expressing mRNA for the receptor remains constant, but the number of Type III neurons expressing transcripts for the 5-HT 1B receptor increased from 41% to 78%. Consistent with this observation, Ferguson and co-workers reported that chronic mild stress increased the expression of 5-HT 1B receptors on the terminals of nucleus accumbens neurons that project to the ventral tegmental area (Ferguson et al, 2009). …”

Section: Discussionmentioning

confidence: 60%

Differential distribution of serotonin receptor subtypes in BNSTALG neurons: Modulation by unpredictable shock stress

et al. 2012

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The bed nucleus of the stria terminalis (BNST) plays a critical role in regulating the behavioral response to stress. Stressors that activate the BNST also activate serotonergic (5-HT) systems. Hence, maladaptive changes of 5-HT receptor expression may contribute to stress-induced anxiety disorders. The BNST contains three neuronal types, Type I – III neurons. However, little is known about 5-HT receptor subtypes mRNA expression in these neurons, or whether it can be modulated by stress. Whole-cell patch clamp recording from Type I – III neurons was used in conjunction with single cell RT-PCR to characterize 5-HT receptor mRNA expression, and examine the effects of stress on this expression. We report that Type I neurons expressed mRNA transcripts predominantly for 5-HT1A and 5-HT7 receptors. Type II neurons expressed transcripts for every 5-HT receptor except the 5-HT2C receptor. Type II neurons were divided into three sub-populations: Type IIA in which transcripts for 5-HT3 and 5-HT7 receptors predominate, Type IIB that mainly express 5-HT1B and 5-HT4 receptor transcripts, and Type IIC in which transcripts for 5-HT1A and 5-HT2A receptors predominate. Type III neurons were also subdivided into two sub-populations; one that predominantly expressed transcripts for 5-HT1A, 5-HT1B and 5-HT2A receptors, and another that mainly expressed transcripts for 5-HT2C receptor. Unpredictable shock stress (USS) caused a long-lasting increase in anxiety-like behavior, and a concomitant decrease in 5-HT1A transcript expression in Type I – III neurons, as well as an up-regulation of a transcriptional repressor of 5-HT1A gene expression, deformed epidermal autoregulatory factor 1(Deaf-1). Significantly USS decreased 5-HT1A protein level, and increased the level of Deaf-1. USS also increased 5-HT1B transcript expression in Type III neurons, as well as 5-HT7 expression in Type I and II neurons. These data suggest that cell type-specific disruption of 5-HT receptor expression in BNSTALG neurons may contribute to stress-induced anxiety disorders.

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Section: Discussionmentioning

confidence: 60%

Differential distribution of serotonin receptor subtypes in BNSTALG neurons: Modulation by unpredictable shock stress

et al. 2012

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“…As animal work has indicated that knocking out 5-HT 1B receptors in mice is associated with increased cocaine self administration (9) and 5-HT 1B receptor over-expression in rats is associated with stress-related stimulant responsiveness (14), there are data to suggest that CD individuals would show either increases or decreases in 5-HT 1B receptors. Given this ambiguity and the unknown effects of cocaine on the 5-HT 1B receptor in humans, the current work could provide evidence for a mechanism in humans and future development by either showing an increase in 5-HT 1B receptor availability in CD, which would support a model of 5-HT 1B sensitization in CD, or a decrease that would support a desensitized model of 5-HT 1B within reward-related brain regions in chronic CD.…”

Section: Introductionmentioning

confidence: 99%

Reductions in Brain 5-HT1B Receptor Availability in Primarily Cocaine-Dependent Humans

Matuskey

Bhagwagar

Planeta

et al. 2014

Biological Psychiatry

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Background Preclinical evidence implicates the 5-HT1B receptor in cocaine’s effects. This study explores 5-HT1B in humans by examining receptor availability in vivo with primary cocaine-dependent (CD) subjects using positron emission tomography (PET). Methods Fourteen medically healthy CD subjects (mean age=41±6 yrs) were compared to 14 age-matched healthy control subjects (41±8 yrs) with no past or current history of cocaine or other illicit substance abuse. Participants received an MRI and then a PET scan with the highly selective 5HT1B tracer, [11C]P943, for purposes of quantifying regional binding potential (BPND). Voxel-based morphometry (VBM) and gray matter masking (GMM) were also employed to control for potential partial volume effects. Results [11C]P943 PET imaging data in nine candidate regions (amygdala, anterior cingulate cortex, caudate, frontal cortex, hypothalamus, pallidum, putamen, thalamus and ventral striatum) showed significant or nearly significant reductions of BPND in CD subjects in three regions, including the anterior cingulate (−16%; P<0.01), hypothalamus (−16%, P=0.03) and frontal cortex (−7%, P=0.08). VBM showed significant gray matter reductions in the frontal cortex of CD subjects. After GMM, statistically significant reductions in [11C]P943 BPND were either retained (anterior cingulate, −14%, p=0.01; hypothalamus, −20%, P<0.01) or achieved (frontal cortex, −14%, p<0.01). Whole brain voxel-wise parameter estimation confirmed these results. Secondary analyses were also significant in some regions for years of cocaine and daily tobacco use. Conclusions The reductions found in this study suggest that 5-HT1B receptors may contribute to the etiology and/or expression of cocaine dependence and potentially represent a target for medication development.

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“…We have previously observed an interaction between coincident exposure to mild stress and increased 5-HT 1B receptor expression in NAccSh projection neurons that facilitates the behavioral effects of exposure to drugs of abuse (Ferguson et al, 2009), suggesting an interplay between the stress response and 5-HT 1B receptor overexpression. These interactions between 5-HT 1B receptors and stress have been observed in the early stages of psychostimulant-related behavioral plasticity (Neumaier et al, 2002b; Ferguson et al, 2009; Neumaier et al, 2009; Hoplight et al, 2007; Furay et al, 2011) and we are now examining the effect of 5-HT 1B receptors in stress-induced reinstatement of cocaine seeking.…”

Section: Introductionmentioning

confidence: 99%

Differential effect of viral overexpression of nucleus accumbens shell 5-HT1B receptors on stress- and cocaine priming-induced reinstatement of cocaine seeking

Nair

Furay

Liu

et al. 2013

Pharmacology Biochemistry and Behavior

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5-HT1B receptors are densely expressed on terminals of medium spiny neurons projecting from the nucleus accumbens shell (NAccSh) to the ventral tegmental area, where 5-HT1B receptors modulate GABA release directly, and firing of dopaminergic neurons indirectly. While interactions between NAccSh 5-HT1B receptors and stress have been reported in early stages of psychostimulant-induced neuroadaptations, specifically psychomotor sensitization, the effect of this interaction on later stages of drug seeking is currently unknown. Here, we examined the effect of herpes simplex virus (HSV)-mediated overexpression of NAccSh 5-HT1B receptors on reinstatement of cocaine seeking induced by exposure to stress or a cocaine prime. Rats were trained to self-administer cocaine (0.75 mg/kg/infusion) and the operant response was extinguished. Rats were then injected with viral vector expressing 5-HT1B and green fluorescent protein (GFP) or GFP alone into the NAccSh. The effect of 5-HT1B receptor overexpression was assessed on reinstatement induced by intermittent footshock (0.5 mA for 15 minutes) or a cocaine prime (10 mg/kg, ip). Results indicate that NAccSh 5-HT1B receptor overexpression had no effect on footshock reinstatement while significantly decreasing cocaine priming-induced reinstatement. We also found that NAccSh overexpression of 5-HT1B receptors had no effect on saccharin intake following social defeat stress. These results suggest that the efficacy of pharmacological agents targeting 5-HT1B receptors for the treatment of cocaine relapse will depend largely on the nature of the reinstating stimulus. Taken together with previous results it appears that NAccSh 5-HT1B receptors influence stress responses in early, but not in the later stages of psychostimulant-induced neuroadaptations.

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Pairing mild stress with increased serotonin‐1B receptor expression in the nucleus accumbens increases susceptibility to amphetamine

Cited by 16 publications

References 38 publications

Differential distribution of serotonin receptor subtypes in BNSTALG neurons: Modulation by unpredictable shock stress

Differential distribution of serotonin receptor subtypes in BNSTALG neurons: Modulation by unpredictable shock stress

Reductions in Brain 5-HT1B Receptor Availability in Primarily Cocaine-Dependent Humans

Differential effect of viral overexpression of nucleus accumbens shell 5-HT1B receptors on stress- and cocaine priming-induced reinstatement of cocaine seeking

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