Differential Roles of 5-HT Receptor Subtypes in Cue and Cocaine Reinstatement of Cocaine-Seeking Behavior in Rats

Burmeister, J; Lungren, Erin M.; Kirschner, Kenneth F.; Neisewander, Janet L.

doi:10.1038/sj.npp.1300346

Cited by 99 publications

(92 citation statements)

References 44 publications

(52 reference statements)

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“…Interestingly this dose is lower than that typically required to reduce cocaine self-administration, locomotor activity, and especially cocaine-induced reinstatement (Grottick et al, 2000). The 5-HT releaser fenfluramine reduced reinstatement of responding elicited by response contingent presentations of discrete cues that had been paired with cocaine (Burmeister et al, 2004). That effect was blocked by SB242084 providing further evidence that stimulation of 5-HT 2C receptors inhibits cue-induced reinstatement.…”

Section: Discussionmentioning

confidence: 82%

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

Fletcher

Rizos

Sinyard

et al. 2007

Neuropsychopharmacol

112

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Previously, we showed that the 5-HT 2C receptor agonist Ro60-0175 reduces cocaine self-administration, and the ability of cocaine to reinstate responding after extinction of drug-seeking behavior. The present experiments extended these findings further by determining whether the effects of Ro60-0175 on self-administration were sustained with repeated treatment, and whether Ro60-0175 altered reinstatement induced by the pharmacological stressor yohimbine, or by the context in which self-administration occurred. In Experiment 1, Ro60-0175 (1 mg/kg, s.c.) reduced cocaine (0.25 mg/infusion) self-administration maintained by a progressive ratio schedule. This reduction was sustained over eight daily injections. In Experiment 2, rats self-administered cocaine in daily 2 h sessions for 15 days on a FR1 schedule. Following extinction, yohimbine (1 mg/kg, i.p.) reinstated responding, and this effect was reduced dose dependently by Ro60-0175 (0.3-3 mg/kg, s.c.). In Experiment 3, rats were trained to respond for cocaine on a FR1 schedule in a distinct environmental context (A); responding was then extinguished in a different context (B). Reinstatement tests occurred in either context A or B.Responding was reinstated only when rats were tested in the original self-administration context (A). This reinstatement was reduced dose dependently by Ro60-0175. All effects of Ro60-0175 were blocked by the 5-HT 2C receptor antagonist SB242084. Thus, Ro60-0175, acting via 5-HT 2C receptors, reduces cocaine self-administration and cocaine-seeking triggered by a stressor and by drug-associated cues. The effects of Ro60-0175 do not exhibit tolerance within the 8-day test period. These results indicate that selective 5-HT 2C receptor agonists may be a useful pharmacological strategy for treatment of drug abuse.

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Section: Discussionmentioning

confidence: 82%

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

Fletcher

Rizos

Sinyard

et al. 2007

Neuropsychopharmacol

112

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“…For instance, SCH-23390 is a full-efficacy agonist at 5-HT 2C receptors (Millan et al, 2001), which have been implicated in cocaine abuse-related behaviors (Callahan and Cunningham, 1995;Grottick et al, 2000;Fletcher et al, 2002Fletcher et al, , 2004Burmeister et al, 2004;Filip et al, 2004). At the concentrations used intracranially, SCH-23390 also functions as an antagonist for G protein-coupled, inwardly rectifying potassium channels (GIRK; Kuzhikandathil and Oxford, 2002).…”

Section: Discussionmentioning

confidence: 99%

Effects of SCH-23390 Infused into the Amygdala or Adjacent Cortex and Basal Ganglia on Cocaine Seeking and Self-Administration in Rats

Alleweireldt

Hobbs

Taylor

et al. 2005

Neuropsychopharmacol

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Amygdala D1 receptors have been implicated in the motivating effects of cocaine-conditioned cues and cocaine itself, but the specific nucleus involved is unclear. Thus, we infused the D1 antagonist, SCH-23390, into the rostral basolateral amygdala (rBLA), caudal basolateral amygdala (cBLA), or central amygdala (CEA), and tested its effects on self-administration of cocaine, as well as reinstatement of extinguished cocaine-seeking behavior by cocaine-conditioned cues or cocaine itself. Two anatomical controls, the posterior regions of basal ganglia (BG) and somatosensory/insular cortices (CTX), were also examined. Cocaine self-administration was increased and cue and cocaine reinstatement were decreased by SCH-23390 infusion into every region when examined across the hour test session, with the exception that cBLA infusion did not alter cocaine reinstatement. In the first 20 min of the session, when SCH-23390 was more localized in the target sites, self-administration was increased by infusion into the CEA, cBLA, BG, and CTX, with lesser increases in the rBLA. Cocaine reinstatement was attenuated during the first 20 min only by infusion into the CEA, rBLA, and CTX. Cue reinstatement was not reliably observed in the first 20 min, but there was a trend for attenuation by infusion into the cBLA, and surprisingly, significant attenuations in the BG and CTX. The findings suggest that D1 receptors in subregions of the amygdala play differential roles in the reinforcing/motivational effects of cocaine, while the cue reinstatement effects are less clear. Further research is needed to examine the novel findings that neighboring regions of the BG and CTX may play a role in motivation for cocaine.

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“…Hence, SERT blockade by cocaine results into constitutive increased extracellular 5-HT levels, and secondary, activation of various 5-HT receptors that directly, or indirectly via the dopaminergic or noradrenergic systems, may influence the rewarding and motivational properties of cocaine (Acosta et al 2005;Burmeister et al 2004). Individual differences in central 5-HT levels have been proposed to influence personality in a trait-like manner (Serretti et al 2006), suggesting that such individual differences are constitutive (Highley and Linnoila 1997) and genetically determined.…”

Section: Introductionmentioning

confidence: 99%

Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats

et al. 2008

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Rationale While individual differences in vulnerability to psychostimulants have been largely attributed to dopaminergic neurotransmission, the role of serotonin is not fully understood. Objectives To study the rewarding and motivational properties of cocaine in the serotonin transporter knockout (SERT −/− ) rat and the involvement of compensatory changes in 5-HT 1A receptor function are the objectives of the study. Materials and methodsThe SERT −/− rat was tested for cocaine-induced locomotor activity, cocaine-induced conditioned place preference, and intravenous cocaine selfadministration. In addition, the function and expression of 5-HT 1A receptors was assessed using telemetry and autoradiography, respectively, and the effect of 5-HT 1A receptor ligands on cocaine's psychomotor effects were studied.Results Cocaine-induced hyperactivity and conditioned place preference, as well as intravenous cocaine selfadministration were enhanced in SERT −/− rats. Furthermore,

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Differential Roles of 5-HT Receptor Subtypes in Cue and Cocaine Reinstatement of Cocaine-Seeking Behavior in Rats

Cited by 99 publications

References 44 publications

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

Effects of SCH-23390 Infused into the Amygdala or Adjacent Cortex and Basal Ganglia on Cocaine Seeking and Self-Administration in Rats

Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats

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