Journal
PHARMACOLOGICAL REPORTS
Volume 65, Issue 4, Pages 813-822Publisher
POLISH ACAD SCIENCES INST PHARMACOLOGY
DOI: 10.1016/S1734-1140(13)71062-4
Keywords
5-HT1B receptor; amphetamine self-administration; reinstatement of amphetamine-seeking behavior; rat
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Funding
- Ministry of Science and Higher Education (Warszawa, Poland) [N N401 050836]
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Background: Numerous studies have indicated that serotonin (5-HT)(1B) receptor ligands affect the behavioral effects of psychostimulants (cocaine, amphetamine), including the reinforcing activities of these drugs. Methods: To substantiate a role for those receptors in incentive motivation for amphetamine, we used the extinction/reinstatement model to examine the effects of the 5-HT1B receptor ligands on the reinstatement of extinguished amphetamine-seeking behavior. Rats trained to self-administer amphetamine (0.06 mg/kg/infusion) subsequently underwent the extinction procedure. These rats were then tested for the amphetamine-primed or amphetamine-associated cue-induced reinstatement of extinguished amphetamine-seeking behavior. Results: The 5-HT1B receptor antagonist SB 216641 (5-7.5 mg/kg) attenuated the amphetamine (1.5 mg/kg)- and the amphetamine-associated cue combined with the threshold dose of amphetamine (0.5 mg/kg)-induced reinstatement of amphetamine-seeking behavior. The 5-HT1B receptor agonist CP 94253 (1.25-5 mg/kg) also inhibited the amphetamine-seeking behavior induced by amphetamine (1.5 mg/kg) but not by the cue combined with the threshold dose of amphetamine. The inhibitory effect of CP 94253 on amphetamine-seeking behavior remained unaffected by the 5-HT1B receptor antagonist. Conclusion: Our results indicate that tonic activation of 5-HT1B receptors is involved in amphetamine- and cue-induced reinstatement of amphetamine-seeking behavior and that the inhibitory effects of 5-HT1B receptor antagonists on these phenomena are directly related to the motivational aspects of amphetamine abuse. The inhibitory effect of CP 94253 on amphetamine-seeking behavior seems to be unrelated to 5-HT1B receptor activation and may result from a general reduction of motivation.
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