MODULATION OF THE THC EFFECTS IN ADOLESCENT RODENTS BY AN A<SUB>2A</SUB> RECEPTOR AGONIST

Numerous studies have shown that adolescence is a period of particular vulnerability to the adverse effects of cannabis. However, the neurobiological processes underlying these effects remain poorly understood. In this context, the present study aimed to evaluate whether the adenosine A_2A receptor (A_2AR) plays a relevant role in the acute and long-term effects of adolescence exposure to Δ⁹-tetrahydrocannabinol (THC), the main psychoactive component of cannabis.
In vivo electrophysiological recordings revealed that a single administration of the A_2AR agonist CGS21680 (0.05 mg/kg, i.v.) to late adolescent rats reduced the THC-induced (2 mg/kg, i.v.) dopaminergic hyperactivity in the ventral tegmental area, a key brain area involved in rewarding processing and emotional regulation. These findings suggested that concomitant activation of A_2AR might prevent some long-term behavioral consequences of THC exposure during adolescence. Therefore, we tested whether chronic treatment with CGS21680 (0.1 mg/kg/day, 32 days) could prevent the sociability deficits previously described in adult mice following chronic THC exposure during adolescence (5 mg/kg/day, 32 days, from PND28 to PND60). Our results indicate that chronic CGS21680 treatment did not attenuate the long-term detrimental effects of adolescence THC exposure on sociability in adulthood (PND112). However, CGS21680 treatment during adolescence induced long-term memory and sociability deficits in mice not exposed to THC. No significant differences were observed between male and female animals in any experimental condition. In conclusion, our findings suggest that A_2AR plays a role in the development of cognitive and social behaviors during adolescence and may modulate acute, but not long-term, effects of THC.