Abstract
Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy (OBX) model of depression with intravenous drug self-administration procedure to verify whether depressive-like rats displayed altered voluntary intake of the CB1 receptor agonist WIN55,212-2 (WIN, 12.5 μg/kg/infusion). To this aim, olfactory-bulbectomized (OBX) and sham-operated (SHAM) Lister Hooded rats were allowed to self-administer WIN by lever-pressing under a continuous [fixed ratio 1 (FR-1)] schedule of reinforcement in 2 h daily sessions. Data showed that both OBX and SHAM rats developed stable WIN intake; yet, responses in OBX were constantly higher than in SHAM rats soon after the first week of training. In addition, OBX rats took significantly longer to extinguish the drug-seeking behavior after vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist, CGS-12066B (2.5–10 mg/kg), did not significantly modify WIN intake in OBX and SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and 15 mg/kg) did not alter responses in parallel groups of OBX and SHAM Sprague Dawley rats self-administering methamphetamine under higher (FR-2) reinforcement schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus accumbens (NAc) of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats. Altogether, our findings suggest that a depressive-like state may alter cannabinoid CB1 receptor agonist-induced brain reward function and that a dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN self-administration in OBX rats.
Highlights
Many psychiatric disorders including depression, schizophrenia, and anxiety are frequently associated to drug addiction (Langas et al, 2010; Testa et al, 2013)
Dopamine levels in the nucleus accumbens (NAc) of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats
BEHAVIORAL PROFILE AFTER OBX SURGERY (LISTER HOODED RATS) To verify the development of a depressive-like phenotype in OBX lesioned animals, basal behavioral differences between SHAM and OBX rats were established by measuring sucrose preference and locomotor activity
Summary
Many psychiatric disorders including depression, schizophrenia, and anxiety are frequently associated to drug addiction (Langas et al, 2010; Testa et al, 2013). A genetically conditioned hypersensitivity to elicit cannabis dependence was evaluated in a depressive population, and the outcome was not fully conclusive authors suggested that the links between cannabis use and depressive symptoms are conditional on the individual’s genetic makeup (Otten and Engels, 2013). Social difficulties such as limited economical resources, impaired interpersonal skills, social isolation, or stressful events may trigger both depression and cannabis abuse (Baker et al, 2010). Cannabis use has been proposed to serve as a self-medication in depressed patients (Degenhardt et al, 2003), some studies excluded that www.frontiersin.org
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
