Age-dependent effects of κ-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate–putamen: an in vivo microdialysis study

Cortez, Anthony M.; Charntikov, Sergios; Der-Ghazarian, Taleen; Horn, Leslie R.; Crawford, Cynthia A.; McDougall, Sanders A.

doi:10.1016/j.neuroscience.2010.04.052

Cited by 11 publications

(9 citation statements)

References 73 publications

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“…Our findings are consistent with previously reported KOR-mediated reduction in BLA excitability in adolescents (Huge, Rammes, Beyer, Zieglgansberger, & Azad, 2009). Ultimately, these neurophysiological effects would produce an anxiolytic effect in adolescents, consistent with previously demonstrated anxiolytic effects of KOR agonists in stress-naïve adolescents (Alexeeva, Nazarova, & Sudakov, 2012;Anderson, Morales, Spear, & Varlinskaya, 2014;Chen et al, 2015;Collins, Zavala, Nazarian, & McDougall, 2000;Cortez et al, 2010;McDougall, Garmsen, Meier, & Crawford, 1997;Nizhnikov, Pautassi, Varlinskaya, Rahmani, & Spear, 2012;Privette & Terrian, 1995).…”

Section: Introductionsupporting

confidence: 85%

Adolescent forced swim stress increases social anxiety-like behaviors and alters the dynorphin/kappa opioid receptor system in the basolateral amygdala of males

Johnson

Deak

Diaz

2019

Preprint

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Adolescence is a developmental period marked by robust neural alterations and heightened vulnerability to stress, a factor that is highly associated with increased risk for emotional processing deficits, such as anxiety. Stress-induced upregulation of the dynorphin/kappa opioid receptor (DYN/KOR) system is thought to, in part, underlie the negative affect associated with stress. The basolateral amygdala (BLA) is a key structure involved in anxiety, and neuromodulatory systems, such as the DYN/KOR system, can 1) regulate BLA neural activity in an age-dependent manner in stress-naïve animals and 2) underlie stress-induced anxiety in adults. However, the role of the DYN/KOR system in modulating stress-induced anxiety in adolescents is unknown. To test this, we examined the impact of an acute, 2-day forced swim stress (FSS -10 min each day) on adolescent (~postnatal day (P) 35) and adult Sprague-Dawley rats (~P70), followed by behavioral, molecular and electrophysiological assessment 24 hours following FSS. Adolescent males, but not adult males or females of either age, demonstrated social anxiety-like behavioral alterations indexed via significantly reduced social investigation and preference when tested 24 hours following FSS. Conversely, adult males exhibited increased social preference. While there were no FSS-induced changes in expression of genes related to the DYN/KOR system in the BLA, these behavioral alterations were associated with a robust switch in BLA KOR function. Specifically, while the KOR agonist, U69593, significantly increased GABA transmission in the BLA of non-stressed adolescent males, U69593 significantly inhibited BLA GABA transmission in stressed adolescent males, consistent with the observed anxiogenic phenotype in stressed adolescent males. This is the first study to demonstrate a KOR-dependent mechanism that may contribute to stress-induced social anxiety in adolescent males. Importantly, these findings provide evidence for potential KOR-dependent mechanisms that may contribute to pathophysiological interactions with subsequent stress challenges.

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Section: Introductionsupporting

confidence: 85%

Adolescent forced swim stress increases social anxiety-like behaviors and alters the dynorphin/kappa opioid receptor system in the basolateral amygdala of males

Johnson

Deak

Diaz

2019

Preprint

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“…For example, administration of various KOR agonists attenuated psychostimulant-induced locomotor activity in adults but not preweanling rats (McDougall et al 1997; Collins et al 2000). Likewise, U50,488 attenuated cocaine-induced dopamine release in adults but not preweanling rats (Cortez et al 2010). Although at least one study has shown that KOR agonists can also produce conditioned odor aversions in infant rat pups (Barr et al 1994), in other work, an ontogenetic switch has been reported in the effects of KOR agonists, with DYN shown to be a powerful appetitive reinforcer in neonatal rats (Petrov et al 2006), in contrast to the aversive properties of KOR agonists consistently demonstrated in adult rats.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological activation of kappa opioid receptors: aversive effects in adolescent and adult male rats

2013

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Rationale The dynorphin (DYN)/kappa opioid receptor (KOR) system is involved in the dysphoric properties of drugs of abuse. Given that adolescents show reduced sensitivity to aversive effects of many drugs, alterations in the DYN/KOR system may contribute to the prevalence of drug use during adolescence. Objectives The present study was designed to assess dysphoric properties of a selective kappa agonist, U62,066, in adolescent and adult rats using both conditioned taste aversion (CTA) and conditioned place aversion (CPA) paradigms. Methods For CTA, water-restricted rats were administered U62,066 following 30 min access to a saccharin solution, with subsequent saccharin consumption used to index aversion. For CPA, animals were allowed access to both compartments of a two-compartment chamber for a 15-minute pre- and post-conditioning test. For conditioning, subjects were administered U62,066 prior to confinement to one side of the chamber and saline prior to confinement to the other side for a total of four pairings. Results Overall, adolescents displayed reduced sensitivity to the kappa agonist relative to adults. Adults demonstrated taste aversions to the 0.2 and 0.3 mg/kg doses of U62,066 whereas adolescents did not display aversions to any tested doses. Adults demonstrated a place aversion to the 0.1 and 0.2 mg/kg dose of U62,066 when paired with the preferred side of the conditioning chamber. Adolescents did not display aversions to any of the doses tested. Conclusions Reduced sensitivity to DYN/KOR system activation during adolescence may be a contributing factor to the age-typical insensitivity to aversive properties of drugs commonly abused by adolescents.

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“…In support, KOR agonists inhibit presynaptic glutamate release and post-synaptic NMDAR potentials [53,75–77] and infusion of KOR agonists to the VTA inhibit midbrain dopaminergic cells [78,79]. Moreover, intra-VTA KOR activation influences psychostimulant effects, decreasing sensitization to cocaine seeking [80] and attenuating cocaine-induced repetitive motor behavior [81]. Recently, cocaine-reinstatement was found to be dampened among squirrel monkeys administered a KOR agonist in a nor-BNI-dependent manner [82].…”

Section: Discussionmentioning

confidence: 99%

Kappa Opioid Receptor-Mediated Disruption of Novel Object Recognition: Relevance for Psychostimulant Treatment

Paris

Reilley²,

McLaughlin³

2012

J Addict Res Ther

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Kappa opioid receptor (KOR) agonists are potentially valuable as therapeutics for the treatment of psychostimulant reward as they suppress dopamine signaling in reward circuitry to repress drug seeking behavior. However, KOR agonists are also associated with sedation and cognitive dysfunction. The extent to which learning and memory disruption or hypolocomotion underlie KOR agonists’ role in counteracting the rewarding effects of psychostimulants is of interest. C57BL/6J mice were pretreated with vehicle (saline, 0.9%), the KOR agonist (trans)-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)-cyclohexyl] benzeneacetamide (U50,488), or the peripherally-restricted agonist D-Phe-D-Phe-D-lle-D-Arg- NH2 (ffir-NH2), through central (i.c.v.) or peripheral (i.p.) routes of administration. Locomotor activity was assessed via activity monitoring chambers and rotorod. Cognitive performance was assessed in a novel object recognition task. Prolonged hypolocomotion was observed following administration of 1.0 and 10.0, but not 0.3 mg/kg U50,488. Central, but not peripheral, administration of ffir-NH2 (a KOR agonist that does not cross the blood-brain barrier) also reduced motor behavior. Systemic pretreatment with the low dose of U50,488 (0.3 mg/kg, i.p.) significantly impaired performance in the novel object recognition task. Likewise, ffir-NH2 significantly reduced novel object recognition after central (i.c.v.), but not peripheral (i.p.), administration. U50,488- and ffir-NH2-mediated deficits in novel object recognition were prevented by pretreatment with KOR antagonists. Cocaine-induced conditioned place preference was subsequently assessed and was reduced by pretreatment with U50,488 (0.3 mg/kg, i.p.). Together, these results suggest that the activation of centrally-located kappa opioid receptors may induce cognitive and mnemonic disruption independent of hypolocomotor effects which may contribute to the KOR-mediated suppression of psychostimulant reward.

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Age-dependent effects of κ-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate–putamen: an in vivo microdialysis study

Cited by 11 publications

References 73 publications

Adolescent forced swim stress increases social anxiety-like behaviors and alters the dynorphin/kappa opioid receptor system in the basolateral amygdala of males

Adolescent forced swim stress increases social anxiety-like behaviors and alters the dynorphin/kappa opioid receptor system in the basolateral amygdala of males

Pharmacological activation of kappa opioid receptors: aversive effects in adolescent and adult male rats

Kappa Opioid Receptor-Mediated Disruption of Novel Object Recognition: Relevance for Psychostimulant Treatment

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