Enhanced self-administration of the CB1 receptor agonist WIN55,212-2 in olfactory bulbectomized rats: evaluation of possible serotonergic and dopaminergic underlying mechanisms.
Petra Amchova, Jana Kučerová, Valentina Giugliano, Zuzana Babinska, Mary T. Zanda, Maria Scherma, Ladislav Dusek, Paola Fadda, Vincenzo Micale, Alexandra Sulcova, Walter Fratta, Liana Fattore
Frontiers in Pharmacology 2014 DOI: 10.3389/fphar.2014.00044 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Lister Hooded and Sprague Dawley rats, olfactory-bulbectomized (OBX) and sham-operated (SHAM) |
| Interventions | WIN55 212-2 CGS-12066B methamphetamine |
| Dose | WIN55,212-2 12.5 μg/kg/infusion; CGS-12066B 2.5-10 mg/kg and 10 and 15 mg/kg |
| Topics | Depression Serotonin |
| Keywords | Win55212-2 Cannabinoid Dopamine Drug dependence Methamphetamine Olfactory bulbectomy |
| Key points | OBX rats self-administered the CB1 agonist WIN55,212-2 more than sham rats and took significantly longer to extinguish drug-seeking after vehicle substitution. The 5-HT1B agonist CGS-12066B did not significantly alter WIN or methamphetamine self-administration, and nucleus accumbens dopamine failed to increase after a WIN challenge in OBX rats, suggesting a dopaminergic rather than 5-HT1B mechanism underlies the enhanced cannabinoid intake. |
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.
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Citations in the library
Cited by 4
- Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia Neurotoxicity Research July 1, 2017
- Crosstalk between the transcriptional regulation of dopamine D2 and cannabinoid CB1 receptors in schizophrenia: Analyses in patients and in perinatal Δ9-tetrahydrocannabinol-exposed rats. Pharmacological Research February 2021
- Cannabis exacerbates depressive symptoms in rat model induced by reserpine. Behavioural Brain Research May 1, 2017
- Delta-9-tetrahydrocannabinol (THC) history fails to affect THC's ability to induce place preferences in rats. Pharmacology, Biochemistry, and Behavior May 2016