Interaction between noradrenaline and corticotrophin-releasing factor in the reinstatement of cocaine seeking in the rat

Brown, Zenya J.; Tribe, Erin; D’souza, Nicole A.; Erb, Suzanne

doi:10.1007/s00213-008-1376-4

Cited by 78 publications

(84 citation statements)

References 46 publications

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“…For example, at higher doses, the alpha2 agonist, clonidine has been shown to saturate presynaptic alpha2 receptors and activate lower affinity post-synaptic receptors, as well as bind to imidazoline I(1) receptor sites (Eglen et al, 1998). This serves to mimic the counterintuitive 'stimulant-like' effects of NE potentially increasing the motivation for cocaine (Feltenstein and See, 2006;Brown et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Guanfacine Effects on Drug Craving and Stress Arousal in Cocaine-Dependent Individuals

Fox

Morgan

Sinha

2014

Neuropsychopharmacol

102

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Currently, no FDA-approved medication exists for the treatment of cocaine use disorder. Furthermore, as women become increasingly more at risk for the consequences of cocaine addiction, the need to establish better-tailored treatment medications is paramount. We examine the effects of the alpha2 adrenergic agonist, guanfacine HCl, on responses to stress and drug cue in a group of cocainedependent men and women who also abuse alcohol and nicotine. Forty early abstinent treatment-seeking cocaine-dependent males and females were randomly assigned to receive either daily placebo (12 M/7 F) or guanfacine (2 or 3 mg) (15 M/6 F) for 3 weeks. In week 4, they participated in a laboratory experiment and were exposed to three 10-min guided imagery conditions (stress/stress, cue/cue, and stress/cue), one per day, consecutively in a random, counterbalanced order. Craving, negative emotion, anxiety, and cardiovascular function were assessed at baseline, immediately following imagery exposure, and at various recovery time points. Guanfacine significantly attenuated cocaine craving, alcohol craving, anxiety, and negative emotion following exposure to all three imagery conditions in females, but not males. Guanfacine did, however, reduce sympathetic tone as well as stress and cue-induced nicotine craving and systolic blood pressure (SBP) in both males and females. These findings highlight sex-specific effects of guanfacine on drug craving, anxiety, and negative mood with significant effects in women and not men. The findings suggest further evaluation of guanfacine in the treatment of cocaine use disorder with a specific focus on sex differences in treatment response.

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Section: Discussionmentioning

confidence: 99%

Sex Differences in Guanfacine Effects on Drug Craving and Stress Arousal in Cocaine-Dependent Individuals

Fox

Morgan

Sinha

2014

Neuropsychopharmacol

102

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“…Furthermore, although the a 2 -AR antagonist yohimbine was able to induce reinstatement in both rats and squirrel monkeys, the effect of a pretreatment with the a 2 -AR agonist clonidine differed between the species. In rats, clonidine had no effect on yohimbine-induced reinstatement (Brown et al, 2009), whereas clonidine dose-dependently attenuated yohimbine-induced reinstatement in squirrel monkeys (Lee et al, 2004). The current study presents another example of differing effects of a noradrenergic manipulation on the behavioral pharmacology of cocaine in nonhuman primates and rodents.…”

Section: Effects Of Dopamine B-hydroxylase Inhibition In Monkeysmentioning

confidence: 65%

Effects of Pharmacologic Dopamine β-Hydroxylase Inhibition on Cocaine-Induced Reinstatement and Dopamine Neurochemistry in Squirrel Monkeys

Cooper¹,

Kimmel²,

Manvich³

et al. 2014

J Pharmacol Exp Ther

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Disulfiram has shown promise as a pharmacotherapy for cocaine dependence in clinical settings, although it has many targets, and the behavioral and molecular mechanisms underlying its efficacy are unclear. One of many biochemical actions of disulfiram is inhibition of dopamine b-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons. Thus, disulfiram simultaneously reduces NE and elevates DA tissue levels in the brain. In rats, both disulfiram and the selective DBH inhibitor nepicastat block cocaine-primed reinstatement, a paradigm which is thought to model some aspects of drug relapse. This is consistent with some clinical results and supports the use of DBH inhibitors for the treatment of cocaine dependence. The present study was conducted to confirm and extend these results in nonhuman primates. Squirrel monkeys trained to self-administer cocaine were pretreated with disulfiram or nepicastat prior to cocaineinduced reinstatement sessions. Neither DBH inhibitor altered cocaine-induced reinstatement. Unexpectedly, nepicastat administered alone induced a modest reinstatement effect in squirrel monkeys, but not in rats. To investigate the neurochemical mechanisms underlying the behavioral results, the effects of DBH inhibition on extracellular DA were analyzed in the nucleus accumbens (NAc) using in vivo microdialysis in squirrel monkeys. Both DBH inhibitors attenuated cocaine-induced DA overflow in the NAc. Hence, the attenuation of cocaine-induced changes in accumbal DA neurochemistry was not associated with altered cocaine-seeking behavior. Overall, the reported behavioral effects of DBH inhibition in rodent models of relapse did not extend to nonhuman primates under the conditions used in the current studies.

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“…In monkeys, the reinstating effects of yohimbine were blocked by clonidine and replicated with a selective a2AR antagonist (Lee et al, 2004), implicating the a2AR. Conversely, clonidine had no effect on yohimbineprimed reinstatement in rats (Brown et al, 2009), suggesting a contribution of nonadrenergic receptors, although the preferential a2aAR-selective agonist guanfacine did reduce yohimbine-primed reinstatement in this species (Buffalari et al, 2012).…”

Section: Self-administrationmentioning

confidence: 75%

“…Stress, cues previously associated with the drug, or the noncontingent administration of the drug itself can trigger drug-seeking behaviors. Interestingly, NE alone has been shown to reinstate cocaine seeking when administered intracerebroventricularly (Brown et al, 2009). The authors attributed this phenomenon to a stress effect because it was associated with activation of neurons in the BNST and central amygdala that are part of the brain's stress pathway (Brown et al, 2011).…”

Section: Self-administrationmentioning

confidence: 99%

Adrenaline Rush: The Role of Adrenergic Receptors in Stimulant-Induced Behaviors

Schmidt

Weinshenker

2014

Mol Pharmacol

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Psychostimulants, such as cocaine and amphetamines, act primarily through the monoamine neurotransmitters dopamine (DA), norepinephrine, and serotonin. Although stimulant addiction research has largely focused on DA, medication development efforts targeting the dopaminergic system have thus far been unsuccessful, leading to alternative strategies aimed at abating stimulant abuse. Noradrenergic compounds have shown promise in altering the behavioral effects of stimulants in rodents, nonhuman primates, and humans. In this review, we discuss the contribution of each adrenergic receptor (AR) subtype (a1, a2, and b) to five stimulant-induced behaviors relevant to addiction: locomotor activity, conditioned place preference, anxiety, discrimination, and self-administration. AR manipulation has diverse effects on these behaviors; each subtype profoundly influences outcomes in some paradigms but is inconsequential in others. The functional neuroanatomy and intracellular signaling mechanisms underlying the impact of AR activation/blockade on these behaviors remain largely unknown, presenting a new frontier for research on psychostimulant-AR interactions.

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Interaction between noradrenaline and corticotrophin-releasing factor in the reinstatement of cocaine seeking in the rat

Abstract: Together, the present findings suggest a functional interaction between NA and CRF systems in mediating stress-induced reinstatement of cocaine seeking, whereby activation of CRF receptors occurs subsequent to, and downstream of, the sites of action of NA.

Cited by 78 publications

References 46 publications

Sex Differences in Guanfacine Effects on Drug Craving and Stress Arousal in Cocaine-Dependent Individuals

Sex Differences in Guanfacine Effects on Drug Craving and Stress Arousal in Cocaine-Dependent Individuals

Effects of Pharmacologic Dopamine β-Hydroxylase Inhibition on Cocaine-Induced Reinstatement and Dopamine Neurochemistry in Squirrel Monkeys

Adrenaline Rush: The Role of Adrenergic Receptors in Stimulant-Induced Behaviors

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