Involvement of 5-HT1A and 5-HT1B Receptors in Modulation of Methamphetamine I.V. Self-Administration in Rats

Authors

ŠULCOVÁ Alexandra NOVÁKOVÁ Jana VINKLEROVÁ Jana

Year of publication 2002
Type Article in Proceedings
Conference The 7th NIDA International Forum
MU Faculty or unit

Faculty of Medicine

Citation
Field Pharmacology and pharmaceutical chemistry
Keywords methamphetamine; self-administration; 5-HT1A receptor; 5-HT1B receptor; rats
Description Methamphetamine acts neurotoxically in the brain, also on the serotonergic system, what is believed to endorse its behavioral effects and abuse. Thus, the present study ascertained the effects of 5-HT1A and 5-HT1B receptor ligands on intake of methamphetamine in rats with dependence raised in i. v. self-administration procedure (a fixed-ratio schedule: FR). Rats with stable methamphetamine intake on FR3 were acutely pretreated with serotonergics 15 minutes prior to self-administration session. The intraperitoneal pretreatment used: a) saline solution as a control (2.0 ml/kg, n=6), b) 5-HT1A/B agonist RU24969 (0.5; 1.5 and 4.5 mg/kg, n=13), c) 5-HT1A agonist 8-OH-DPAT (0.3; 1.0 and 3.0 mg/kg, n=6, d) 5-HT1B agonist CGS 12066B (1.0; 5.0 and 15.0 mg/kg, n=10). Statistical analysis was performed by the Wilcoxon matched-pairs signed-ranks test, two-tailed. Agonist of 5-HT1A receptor subtype had no significant influence on methamphetamine intake. The drug intake was partially suppressed by mixed 5-HT1A/B agonist RU24969 and significantly inhibited after the pretreatment with 5-HT1B agonist CGS 12066B. According to the present results the 5-HT1B receptor plasticity seems to play important role for the conditioned reward responding to methamphetamine i. v. self-administration while the 5-HT1A receptor subtype is not involved. These findings correspond well with analogous experience of Fletcher and Korth (Behav Pharmacol, 1999, 10, 183-193) received while testing effects of some other serotonergic ligands on d-amphetamine i.v. self-administration.
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