Effect of Glycogen Synthase Kinase 3-β on the Acquisition & Expression of Intra-Accumbal Amphetamine-Induced Conditioned Place Preference in Rats
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Dopamine (DA) drives incentive learning: learning which is elicited through rewarding stimuli. Irregularities in DA activity are associated with various psychological disorders. Glycogen synthase kinase-3β (GSK3β), a molecule downstream of DA receptors, has been implicated in mediating dopaminergic behaviour, and unbalanced DA activity is associated with concomitant irregularities in GSK3β signaling. Inhibition of this molecule has been noted to attenuate behavioural sensitization, and decrease psychotomimetic behaviour in animals. Few studies have assessed the role of GSK3β in the conditioned place preference (CPP) paradigm, which evaluates the rewarding properties of substances and has been used to model psychosis. CPP can be examined through either acquisition or expression paradigms, which look at the active learning process vs. the recall of learned information respectively. We tested the hypothesis that selective inhibition of GSK3β with SB 216763 will differentially and dose-dependently affect the acquisition and expression of amphetamine (AMPH) CPP, as well as attenuate AMPH locomotor activity in acquisition. All drugs and vehicles were administered via intra-cranial microinfusions into the nucleus accumbens. AMPH was administered at a dose of 20.0 μg/0.5 μl/side. SB 216763 was tested at four doses (0.03, 0.30, 3.00, & 5.00 μg/0.5 μl/side) in both acquisition and expression. We found administering SB 216763 at all doses to attenuate AMPH CPP and locomotor activity in acquisition. At doses 0.30, 3.00, & 5.00 μg/0.5 μl/side, SB 216763 also blocked AMPH CPP at expression. These results lend support to GSK3β’s involvement in incentive learning and DA-mediated behaviours, and suggest its inhibition may differentially affect the acquisition and expression of AMPH CPP.