Nicotine withdrawal and κ-opioid receptors

McCarthy, Michael J.; Zhang, Hailing; Neff, Norton H.; Hadjiconstantinou, Maria

doi:10.1007/s00213-009-1674-5

Cited by 15 publications

(9 citation statements)

References 60 publications

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“…The concomitant diminution of the ability of pCl-DPDPE to inhibit adenylyl cyclase in striatal membranes provides further support for DOPr uncoupling during nicotine withdrawal. The attenuated pCl-DPDPE-stimulated [ 35 S] GTPγS binding is unlikely to be caused by a decrease in G i/o proteins, as basal binding was not different among saline-and nicotine-treated mice at the times studied, and we have not found appreciable changes in the levels of G i1,2,3 and G o proteins in the striatum 24-72 h during nicotine withdrawal (McCarthy et al 2010). Loss of agonist activity, e.g., reduced [ 35 S]GTPγS binding, has been interpreted to indicate receptor desensitization at the Gprotein level (Harrison and Traynor 2003).…”

Section: Discussioncontrasting

confidence: 58%

Desensitization of δ-opioid receptors in nucleus accumbens during nicotine withdrawal

et al. 2010

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Section: Discussioncontrasting

confidence: 58%

Desensitization of δ-opioid receptors in nucleus accumbens during nicotine withdrawal

et al. 2010

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“…Also, Isola et al (2008) reported that withdrawal from chronic nicotine injections diminishes striatal dynorphin content and enhances prodynorphin expression relative to saline-treated controls. Additionally, McCarthy et al (2009) found that striatal KOR coupling decreases over time after nicotine withdrawal, suggesting decreased KOR functionality is associated with the dissipation of nicotine withdrawal. Taken together, these studies support the role of KORs in mediating withdrawal from chronic nicotine exposure.…”

Section: Discussionmentioning

confidence: 97%

Dysregulation of kappa-opioid receptor systems by chronic nicotine modulate the nicotine withdrawal syndrome in an age-dependent manner

et al. 2012

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Rationale The mechanisms that mediate age differences during nicotine withdrawal are unclear. Objective This study compared kappa opioid receptor (KOR) activation in naïve and nicotine-treated adolescent and adult rats using behavioral and neurochemical approaches to study withdrawal. Methods The behavioral models used to assess withdrawal included conditioned place and elevated plus maze procedures. Deficits in dopamine transmission in the nucleus accumbens (NAcc) were examined using microdialysis procedures. Lastly, the effects of KOR stimulation and blockade on physical signs produced upon removal of nicotine were examined in adults. Results Nicotine-treated adults displayed a robust aversion to an environment paired with a KOR agonist versus naïve adults. Neither of the adolescent groups displayed a place aversion. KOR activation produced an increase in anxiety-like behavior that was highest in nicotine-treated adults versus all other groups. KOR activation produced a decrease in NAcc dopamine that was largest in nicotine-treated adults versus all other groups. Lastly, KOR activation facilitated physical signs of upon removal of nicotine and KOR blockade reduced this effect. Conclusion Chronic nicotine enhanced the affective, anxiogenic, and neurochemical effects produced by KOR activation in adult rats. Our data suggest that chronic nicotine elicits an increase in KOR function, and this may contribute to nicotine withdrawal since KOR activation facilitated and KOR blockade prevented withdrawal signs upon removal of nicotine. Given that chronic nicotine facilitated the neurochemical effects of KOR agonists in adults but not adolescents, it is suggested that KOR regulation of mesolimbic dopamine may contribute to age differences in nicotine withdrawal.

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“…Moreover, nor-BNI has been shown to block FSS- (Schindler et al, 2010) and U50,488-induced (McLaughlin et al, 2006) potentiation of cocaine-induced CPP, as well as, social defeat stress- (Land et al, 2009), FSS-, and U50,488-induced (Redila and Chavkin, 2008) reinstatement of cocaine-induced CPP. Furthermore, KOR activation is enhanced in limbic brain regions during nicotine withdrawal (Isola et al, 2008; McCarthy et al, 2010). This suggests that KORs may be a promising focus for the development of therapies to treat or prevent relapse.…”

Section: Discussionmentioning

confidence: 99%

Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats

Grella

Funk

Coen

et al. 2014

Behavioural Brain Research

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Rationale The correlation between stress and smoking is well established. The mechanisms that underlie this relationship are, however, unclear. Recent data suggest the kappa-opioid system is involved in the mediation of negative affective states associated with stress thereby promoting drug addiction and relapse. Pharmacological treatments targeting the kappa opioid system and this mechanism may prove to be useful therapeutics for nicotine addiction in the future. Objectives We sought to determine whether there was a stress-specific role of the kappa opioid system in nicotine seeking behavior. Method Groups of male Long Evans rats were trained to self-administer nicotine intravenously; their operant responding for nicotine was extinguished prior to tests of reinstatement. Pretreatment with systemic injections of the kappa opioid receptor (KOR) antagonist nor-binaltorphimine (nor-BNI) was given prior to tests of stress (systemic injections of yohimbine (YOH)) or cue-induced reinstatement of nicotine seeking. Systemic injections of the KOR agonist U50,488 were also given in a test for reinstatement of nicotine seeking. Results Nor-BNI pretreatment at 1 hr and 24 hrs prior to testing was able to block YOH-induced, but not cue-induced reinstatement of nicotine seeking. U50,488 reinstated nicotine seeking behavior in a dose-dependent manner. Conclusions These findings support the hypothesis that the kappa opioid system is involved in relapse to nicotine seeking induced by stress, but not by conditioned cues. KOR antagonists such as nor-BNI may therefore be useful novel therapeutic agents for decreasing the risk of stress-induced drug relapse.

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Nicotine withdrawal and κ-opioid receptors

Abstract: These observations suggest that KOPr coupling and function are impaired in NAc and CPU during nicotine withdrawal, and imply receptor desensitization. KOPr desensitization might be a mechanism to ameliorate aversive behavioral symptoms, as nicotine withdrawal evolves.

Cited by 15 publications

References 60 publications

Desensitization of δ-opioid receptors in nucleus accumbens during nicotine withdrawal

Desensitization of δ-opioid receptors in nucleus accumbens during nicotine withdrawal

Dysregulation of kappa-opioid receptor systems by chronic nicotine modulate the nicotine withdrawal syndrome in an age-dependent manner

Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats

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