Effects of CP-154,526 on responding during extinction from cocaine self-administration in rats

Gurkovskaya, Olga V.; Goeders, Nicholas E.

doi:10.1016/s0014-2999(01)01465-0

Cited by 16 publications

(15 citation statements)

References 27 publications

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“…5), as previously observed for stress-induced reinstatement(7-11). CP-154,526 has been shown to reduce cue-induced reinstatement of cocaine- and methamphetamine-seeking, as well as extinction responding for cocaine (14, 59-60). We found a trend for reduced reinstatement with another CRF R1 antagonist, antalarmin, at 20 mg/kg (Fig.…”

Section: Discussionmentioning

confidence: 99%

α2 Adrenergic and Imidazoline Receptor Agonists Prevent Cue-Induced Cocaine Seeking

Smith

Aston‐Jones

2011

Biological Psychiatry

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Background Drug-associated cues can elicit stress-like responses in addicted individuals, indicating thatcue- and stress-induceddrug relapse may share some neural mechanisms.It is unknown whetherα2 adrenergic receptor agonists, which are known toattenuate stress-induced reinstatement of drug-seeking in rats,also reduce cue-induced reinstatement. Methods Rats were tested for reinstatement of drug-seekingfollowing cocaine self-administration and extinction. We first evaluated the effects ofclonidine, an agonist at α2 and imidazoline-1 (I1) receptors, on relapse to cocaine-seeking. To explore possible mechanisms of clonidine’s effects, we then tested more specific α2 or I1 agonists, post-synaptic adrenergic receptor (α1 and β) antagonists, andcorticotropin-releasing factor receptor-1 (CRF R1) antagonists. Results We found that clonidine,andthe more selective α2 agonists UK-14,304 and guanfacine, decreased cue-induced reinstatement of cocaine-seeking.The specific I1 receptor agonist moxonidine reduced cue-induced as well as cocaine-induced reinstatement.Clonidine or moxonidine effects on cue-induced reinstatementwere reversed by the selective α2 receptor antagonist RS-79948, indicatinga role for α2 receptors.Prazosin and propranolol, antagonists at the α1and β receptor, respectively, reducedcue-induced reinstatement only when administered in combination. Finally, the CRF R1 antagonist CP-154,526reduced cue-induced reinstatement, as previouslyobservedfor stress-induced reinstatement, indicating possible overlap between stress and cue mechanisms. Conclusions These results indicate that α2 and I1 receptor agonists are novel therapeutic options for prevention of cue-induced cocaine relapse. Given that α2 receptor stimulation is associated with sedation in humans, the I1agonist moxonidineseems to have substantial potential for treating addictive disorders.

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Section: Discussionmentioning

confidence: 99%

α2 Adrenergic and Imidazoline Receptor Agonists Prevent Cue-Induced Cocaine Seeking

Smith

Aston‐Jones

2011

Biological Psychiatry

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“…CRH receptor antagonists have also been demonstrated to attenuate the stress- Shaham et al 1998;Erb and Stewart 1999) and cocaine-induced ) reinstatement of extinguished cocaine-seeking behavior in rats. CP-154,526 pretreatment also decreases the increased responding observed during extinction from cocaine self-administration (Gurkovskaya and Goeders 2001), which is regarded as another animal model of cue-induced cocaine seeking (Weiss et al 2000). CRH receptors have also been shown to be involved in other conditioned behaviors associated with cocaine, including conditioned anxiety (DeVries and Pert 1998) and conditioned HPA axis activation (DeVries et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Potential role for the hypothalamo-pituitary-adrenal axis in the conditioned reinforcer-induced reinstatement of extinguished cocaine seeking in rats

Goeders

Clampitt

2002

Psychopharmacology

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“…Furthermore, responding on the cocaine lever following CP-154,526 treatment was significantly suppressed during the first 15 min of the session, a time period during which rats typically sample the cocaine lever during extinction, suggesting that CRH receptors may also be involved in some of the conditioned effects of cocaine. This latter effect was addressed in a subsequent study (62), in which rats were trained to respond on a multiple schedule of cocaine and food reinforcement, and responding during extinction was used as a model of cue-induced craving. CP-154,526 (20 mg/kg, i.p.)…”

Section: Elevated Plus Maze (Epm)mentioning

confidence: 99%

The Pharmacology of CP‐154,526, a Non‐Peptide Antagonist of the CRH1 Receptor: A Review

2003

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Since CRH has been shown to mediate stress-induced physiological and behavioral changes, it has been hypothesized that CRH receptor antagonists may have therapeutic potential in disorders that involve excessive CRH activity. CP-154,526 and its close analog antalarmin are potent, brain-penetrable, selective nonpeptide CRH1 receptor antagonists that were discovered in an effort to develop compounds with efficacy in CNS disorders precipitated by stress. Since its discovery many investigators have used CP-154,526 as a tool to study the pharmacology of CRH and its receptors and to evaluate its therapeutic potential in a variety of CNS and peripheral disorders. Systemically-administered CP-154,526 has been demonstrated to antagonize CRH-and stress-induced neuroendocrine, neurochemical, electrophysiological, and behavioral effects.These findings support the hypothesis that CRH1 receptor antagonists may have therapeutic utility in a number of neuropsychiatric disorders. CP-154,526, as well as other CRH1 receptor antagonists that have since been discovered, have also shown activity in several preclinical models of anxiety, depression, and substance abuse, while having little effect on locomotor activity and motor function. Although these effects are on occasion inconsistent among different laboratories, clinical evaluation of CRH1 antagonists appears justified on the basis of these and clinical data implicating the involvement of CRH in several CNS disorders. The effects of CRH1 antagonists on cognition, neurodegeneration, inflammation, and the gastrointestinal system have not been as extensively characterized and additional studies will be necessary to evaluate their therapeutic potential in these areas.

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Effects of CP-154,526 on responding during extinction from cocaine self-administration in rats

Cited by 16 publications

References 27 publications

α2 Adrenergic and Imidazoline Receptor Agonists Prevent Cue-Induced Cocaine Seeking

α2 Adrenergic and Imidazoline Receptor Agonists Prevent Cue-Induced Cocaine Seeking

Potential role for the hypothalamo-pituitary-adrenal axis in the conditioned reinforcer-induced reinstatement of extinguished cocaine seeking in rats

The Pharmacology of CP‐154,526, a Non‐Peptide Antagonist of the CRH1 Receptor: A Review

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