(-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine self-administration in rats. (1st August 2018)

• Record Type: Journal Article
• Authors: Manuszak, M.; Harding, W.; Gadhiya, S.; Ranaldi, R.
• Is Part Of: Drug and alcohol dependence. Volume 189(2018)
• Page Start: 49
• Page End: 54
• Publication Date: 2018-08-01
• Subjects: Cocaine -- Substance use disorder -- (-)-Stepholidine -- Drug addiction; Drug abuse -- Periodicals; Alcoholism -- Periodicals; 616.86
• DOI: 10.1016/j.drugalcdep.2018.04.030
• Languages: English
• ISSNs: 0376-8716

Abstract

Highlights: (-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking. (-)-Stepholidine reduces cocaine self-administration/reward. (-)-Stepholidine may have potential as an anti-cocaine relapse treatment. Abstract: Background: Dopamine receptors are implicated in cocaine reward and seeking. We hypothesize that (-)-stepholidine, a dopamine D1/D2/D3 multi-receptor agent, would be effective in reducing cocaine reward and seeking in an animal model. We investigated the effects of (-)-stepholidine in cue-induced reinstatement of cocaine seeking and cocaine self-administration (reward). Methods: Cue-induced reinstatement experiment: Rats were trained to press a lever reinforced by cocaine (1 mg/kg/injection) for 15 consecutive daily sessions, after which the response was extinguished by withholding cocaine and cocaine-paired cues (light and pump activation). This was followed by a cue-induced reinstatement test where subjects were exposed to two cocaine cue presentations and presses on the active lever produced cues. Subjects were treated with one of four (-)-stepholidine doses prior to the reinstatement test. Cocaine self-administration (reward) experiment: Rats were trained to self-administer cocaine under a progressive ratio schedule of reinforcement. After stable breakpoints were established, rats were injected with four doses of (-)-stepholidine prior to testing; each dose was injected prior to a separate test session with no-treatment sessions intervening to re-establish break points. Results: (-)-Stepholidine significantly reduced cue-induced reinstatement of cocaine seeking in a dose-related manner. Additionally, (-)-stepholidine significantly reduced break points for cocaine reward. (-)-Stepholidine did not significantly affect locomotor activity. Conclusions: (-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine reward, suggesting that it may be useful in treating relapse in cocaine addiction.