Wildtype and mice lacking the gene encoding PKCI/HINT 1 (PKC<SUP>-/-</SUP>) were used to assess the involvement of PKCI/HINT1 in regulating basal locomotor activity and the behavioral activating effects of the psychostimulant, amphetamine. PKCl<SUP>-/-</SUP> mice displayed low level of spontaneous locomotion relative to WT littermates. Acute administration of amphetamine significantly increased locomotor activity in WT mice; an effect that was enhanced in PKCl<SUP>-/-</SUP> mice. Microdialysis studies revealed no alteration in basal DA dynamics in the striatum and nucleus accumbens of KO mice. Similarly, the ability of acute amphetamine to increase DA levels in these brain regions was unaltered. However, a dopamine receptor agonist, apomorphine (10mg/kg), was able to induce a significantly higher locomotor activity in PKCI<SUP>-/-</SUP> mice as compared with WT, suggesting there may be a dopaminergic functional change at the postsynaptic site. Our results also revealed that PKCI KO mice showed a less depression and anxiety trait than their litter mate controls (WT), which indicate that PKCI could also play a role in regulating the emotion states of brain. Together, these results indicated that PKCI/HINT1 may have a suppressive role in normal DA neurotransmission, and may also play an important role for the action of psychostimulants in schizophrenia.
NOVEL NEUROLOGICAL FUNCTION OF MPKCI