Inhibition of PKMzeta in the nucleus accumbens core blocks the expression of locomotor sensitization induced by amphetamine

Abstract

Behavioral sensitization is a form of drug-induced, long-lasting, non-associative memory. Protein kinase M zeta (PKMζ) has been shown to play a role in maintaining associative long-term memory in various brain regions. In the present study, rats were pre-exposed to either saline or amphetamine (AMPH) (1 mg/kg, i.p.). After 1 week of drug-free withdrawal period, they were challenged with AMPH (1 mg/kg, i.p.) following a bilateral microinjection of either saline or zeta inhibitory peptide (ZIP) (5 nmole/side) into the NAcc core. In the AMPH pre-exposed group, the ZIP microinjection blocked the enhanced increase of locomotion by AMPH challenge. These results suggest that PKMζ in the NAcc core plays a role in the expression of AMPH-induced locomotor sensitization, and further extend the role of PKMζ in long-term memory to non-associative form of drug-related memory.