BLOCKADE OF NEUROTENSIN-INDUCED MOTOR-ACTIVITY BY INHIBITION PROTEIN-KINASE

The administration of neurotensin into the ventral tegmental area stim ulates dopamine neurons and locomotor activity. Furthermore, when neur otensin is microinjected daily into the ventral tegmental area the mot or stimulant response increases. The role of protein kinases in the mo tor stimulant effect of neurotensin was evaluated by coadministration of the protein kinase inhibitors H8 and H7 into the ventral tegmental area with neurotensin. It was found that the acute motor stimulant eff ect of neurotensin was abolished in a dose-dependent fashion by H8 coa dministration. Neurotensin-induced activity was also blocked by H7. Ho wever, acute motor stimulation following microinjection of the mu opio id, Tyr-d-Ala-Gly-MePhe-Gly(ol) or the potassium channel antagonist ap amin into the ventral tegmental area was not affected by coadministrat ion with H8. The behavioral sensitization produced by daily neurotensi n microinjection into the ventral tegmental area was also prevented by the coadministration of H8. These data indicate that the motor stimul ation produced by acute and repeated neurotensin microinjection into t he ventral tegmental area is dependent upon activation of protein kina se(s). Furthermore, Tyr-d-Ala-Gly-MePhe-Gly(ol) and apamine elicit loc omotion independently of protein kinase(s).