Effect of 4-phenyl-1,2,3,4-tetrahydroisoquinoline on ambulation induced by injection of methamphetamine into the nucleus accumbens in rats.
4-Phenyl-1,2,3,4-tetrahydroisoquinoline (4-PTIQ) has previously been shown to have antagonistic properties to methamphetamine in the spinal cord. Administration of 4-PTIQ (5 mg/kg, s.c.) reduced the ambulation induced by methamphetamine (0.5 mg/kg, s.c.) in rats. Methamphetamine (3 micrograms), injected unilaterally into the nucleus accumbens, increased ambulation. Alone, 4-PTIQ (10 micrograms) failed to elicit ambulation; however, it inhibited the methamphetamine-induced increase in ambulation. The alpha 1-antagonist prazosin (0.5 micrograms) or the beta-antagonist propranolol (3 micrograms) showed no effect on ambulation induced by methamphetamine. Haloperidol (5 ng), which possesses strong dopamine-blocking activity, abolished the ambulation induced by methamphetamine. The drug 4-PTIQ had weak affinity for dopamine D1 and D2 receptors. These results support the possibility that the inhibitory effects of 4-PTIQ on the ambulation-stimulating effects of methamphetamine, are due to blocking of the dopamine-releasing effect of methamphetamine but not due to dopamine blocking effects.
Tateyama
M
M
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Ohta
S
S
Nagao
T
T
Hirobe
M
M
Ono
H
H
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D007267:Injections; D007279:Injections, Subcutaneous; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D044005:Tetrahydroisoquinolines; D008694:Methamphetamine; C074266:4-phenyl-1,2,3,4-tetrahydroisoquinoline; D011433:Propranolol; D006220:Haloperidol; D011224:Prazosin