Altered CB1 receptor-signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine

摘要: Bilateral olfactory bulbectomy in the rat (OBX) induces behavioral, neurochemical, and structural abnormalities similar to those observed human depression that are normalized after chronic, but not acute, treatment with antidepressants. In our study, OBX animals exhibited significant increases both CB(1) receptor density ([(3)H]CP55490 binding) functionality (stimulation of [(35)S]GTPgammaS binding by cannabinoid (CB) agonist WIN 55212-2) at prefrontal cortex (PFC). After chronic fluoxetine (10 mg/kg/day, 14 days, s.c.), OBX-induced hyperactivity open-field test was fully abolished. Interestingly, reversed enhanced CB(1)-receptor signaling PFC following OBX. The CB Delta(9)-tetrahydrocannabinol (5 mg/kg, i.p., 1 day) did produce any behavioral effect sham-operated returned locomotor activity control values rats. As acute administration elicited a rat, it is unlikely regionally selective enhancement receptor-signaling could be related altered behavior. Our findings reinforce utility this animal model further investigating implication endocannabinoid system modulation emotional processes its potential role adaptive responses