Amphetamine stimulates Wnt3 increases in rat nucleus accumbens.

Dopaminergic neurotransmission is thought to be involved in reward-related incentive learning and addictive behaviour. Amphetamine will alter glycogen synthase kinase-3β (GSK-3β) activity by increasing dopamine transporter efflux rates. We investigated the hypothesis that Wnt signalling will be altered in rat nucleus accumbens within 15 min of injection of amphetamine compared with saline. We isolated RNA from the nucleus accumbens and used reverse transcriptase-PCR to screen for altered Wnt expression. We found that amphetamine had no effect on Wnt5a or Wnt7a expression but increased Wnt3. We then measured protein expression of Wnt3, phosphorylated lipoprotein-related peptide 6, GSK-3β phosphorylated at serine-9 and tyrosine-216 and total β-catenin. We found that amphetamine increased Wnt3 protein expression, increased pLRP6 (threonine-1572) levels, increased β-catenin levels, increased GSK-3β phosphorylation at serine-9, consistent with inhibition of GSK-3β activity, and diminished GSK-3β phosphorylation at tyrosine-216. Our data support the hypothesis that proximate Wnt signalling is rapidly activated by amphetamine in the adult rat nucleus accumbens.