Blockade of neurotensin-induced motor activity by inhibition of protein kinase.
The administration of neurotensin into the ventral tegmental area stimulates dopamine neurons and locomotor activity. Furthermore, when neurotensin is microinjected daily into the ventral tegmental area the motor stimulant response increases. The role of protein kinases in the motor 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 effect of neurotensin was abolished in a dose-dependent fashion by H8 coadministration. Neurotensin-induced activity was also blocked by H7. However, acute motor stimulation following microinjection of the mu opioid, Tyr-d-Ala-Gly-MePhe-Gly(ol) or the potassium channel antagonist apamin into the ventral tegmental area was not affected by coadministration with H8. The behavioral sensitization produced by daily neurotensin microinjection into the ventral tegmental area was also prevented by the coadministration of H8. These data indicate that the motor stimulation produced by acute and repeated neurotensin microinjection into the ventral tegmental area is dependent upon activation of protein kinase(s). Furthermore, Tyr-d-Ala-Gly-MePhe-Gly(ol) and apamine elicit locomotion independently of protein kinase(s).
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman.
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Kalivas
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects*; D009496:Neurotensin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013681:Tegmentum Mesencephali / Q000033:anatomy & histology / Q000502:physiology
D000700:Analgesics; D004745:Enkephalins; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001030:Apamin; D009496:Neurotensin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011494:Protein Kinases; D011493:Protein Kinase C