A novel synthetic cathinone, α-pyrrolidinopentiothiophenone (PVT), produces locomotor sensitization in rat: Implications for GSK3β connections in the nucleus accumbens core

A novel psychoactive substance, alpha-pyrrolidinopentiothiophenone (alpha-PVT), is a structural analog to amphetamine. Recently, it has been shown that alpha-PVT has an abuse potential similar to psychomotor stimulants like cocaine or amphetamine. However, it has not been performed yet to determine whether alpha-PVT develops behavioral sensitization, a well-known phenomenon for psychomotor stimulants. In the present study, rats were first pre-exposed to either saline or alpha-PVT (20 mg/kg, IP) with a total of four injections in every 2-3 days of interval. Then, 2-weeks after withdrawal, locomotor activity was measured with a challenge dose (10 mg/kg, IP) of alpha-PVT and the nucleus accumbens core region was taken out. Similar to psychomotor stimulants, repeated administration of alpha-PVT produced locomotor sensitization. Further, the phosphorylation levels of GSK3 beta in the nucleus accumbens core were found to be decreased only in rats with sensitization developed, but not in those with acute or non-sensitized. Correlation analysis revealed that the phosphorylation levels of GSK3 beta have a strong negative correlation with locomotor activity only in rats with alpha-PVT pre-exposed, but not in those with its acute injection. These results suggest that a certain level of change in the phosphorylation levels of GSK3 beta in the nucleus accumbens core may involve in mediating the expression of locomotor sensitization by repeated injection of alpha-PVT in rats.