期刊
JOURNAL OF NEUROCHEMISTRY
卷 108, 期 6, 页码 1423-1433出版社
WILEY
DOI: 10.1111/j.1471-4159.2009.05898.x
关键词
[S-35]GTP gamma S binding; (9)Delta-tetrahydrocannabinol; cannabinoid receptor 1; fluoxetine; olfactory bulbectomy; prefrontal cortex
资金
- Ministerio de Educacion y Ciencia [SAF-2004/00941, SAF-2007/61862]
- Fundacion Mutua Madrilena
- Fundacion Koplowitz
- Plan Nacional de Drogas
- Fundacion UPSA
Bilateral olfactory bulbectomy in the rat (OBX) induces behavioral, neurochemical, and structural abnormalities similar to those observed in human depression that are normalized after chronic, but not acute, treatment with antidepressants. In our study, OBX animals exhibited significant increases in both CB1 receptor density ([H-3]CP55490 binding) and functionality (stimulation of [S-35]GTP gamma S binding by the cannabinoid (CB) agonist WIN 55212-2) at the prefrontal cortex (PFC). After chronic treatment with fluoxetine (10 mg/kg/day, 14 days, s.c.), OBX-induced hyperactivity in the open-field test was fully abolished. Interestingly, chronic fluoxetine fully reversed the enhanced CB1-receptor signaling in PFC observed following OBX. The CB agonist Delta(9)-tetrahydrocannabinol (5 mg/kg, i.p., 1 day) did not produce any behavioral effect in sham-operated animals but returned locomotor activity to control values in OBX rats. As both acute administration of Delta(9)-tetrahydrocannabinol and chronic fluoxetine elicited a similar behavioral effect in the OBX rat, it is not unlikely that the regionally selective enhancement of CB1 receptor-signaling in the PFC could be related with the altered OBX behavior. Our findings reinforce the utility of this animal model to further investigating the implication of the endocannabinoid system in the modulation of emotional processes and its potential role in the adaptive responses to chronic antidepressants.
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