Most cited article - PubMed ID 26431766
Olfactory bulbectomy increases reinstatement of methamphetamine seeking after a forced abstinence in rats
Depression is a psychiatric disorder characterized by a marked decrease in reward sensitivity. By using the olfactory bulbectomy (OBX) model of depression, it was shown that OBX rats display enhanced drug-taking and seeking behaviors in a self-administration paradigm than sham-operated (SHAM) controls, and sex is an important regulating factor. To reveal potential strain effects, we compared the operant behavior of male and female Sprague-Dawley and Wistar OBX and SHAM rats trained to self-administer palatable food pellets. Results showed that Sprague-Dawley OBX rats of both sexes exhibited lower operant responding rates and food intake than SHAM controls. Food restriction increased responding in both OBX and SHAM groups. Female rats responded more than males, but the OBX lesion abolished this effect. In Wistar rats, bulbectomy lowered food self-administration only during the last training days. Food self-administration was not significantly affected in Wistar rats by sex. In summary, this study showed that bulbectomy significantly reduces operant responding and food intake in male and female Sprague-Dawley rats while inducing a mild reducing effect only in the Wistar strain. Strain-dependent effects were also observed in the modulating role of sex and food restriction on operant responding and palatable food intake.
- Keywords
- depression, olfactory bulbectomy, reward, self-administration, sex, strain,
- Publication type
- Journal Article MeSH
OBJECTIVE: Addiction is a chronic disease with limited pharmacological options for intervention. Focusing on reducing glutamate levels in the brain seems to be a promising strategy in addiction treatment research. Our research aimed to evaluate the effects of CNQX, an antagonist that targets AMPA and kainate glutamatergic receptors while also exhibiting affinity for the NMDA receptor, especially by modulating its glycine site. We conducted this assessment on the self-administration of nicotine and methamphetamine via intravenous (IV) administration in rats. METHODS: An operant IV self-administration model was used in male Wistar rats. When animals maintained a stable intake of nicotine or methamphetamine, we administered a single injection of CNQX (in the dose of 3 or 6 mg/kg IV) to evaluate its effect on drug intake. Subsequently, the rats were forced to abstain by staying in their home cages for 2 weeks. The period of abstinence was followed by a context-induced relapse-like session before which animals were pretreated with the injection of CNQX (3 or 6 mg/kg IV) to evaluate its effect on drug seeking. RESULTS: CNQX significantly reduced nicotine intake during the maintenance phase, but no effect was revealed on nicotine seeking after forced abstinence. CNQX did not affect methamphetamine taking or seeking. CONCLUSION: The effect of reducing nicotine taking but not seeking could be explained by different involvement of glutamatergic receptors in various stages of nicotine dependence.
- Keywords
- AMPA/kainate receptor, CNQX, methamphetamine, nicotine, relapse, self-administration,
- Publication type
- Journal Article MeSH