Differentiation of the inhibitory effects of calcium antagonists on abnormal behaviors induced by methamphetamine or phencyclidine.
The abnormal behaviors induced by methamphetamine (MAP: 1 mg/kg) or phencyclidine (PCP: 10 mg/kg) were measured using behavioral analysis following the microinjection of one of three calcium (Ca) antagonists (nifedipine: Nif, nicardipine: Nic and flunarizine: Flu) into the rat caudate putamen or amygdala. The intraperitoneal administration of MAP or PCP induced abnormal behaviors in a time-dependent manner; the maximum locomotor activity was measured 30-45 min after the administration of MAP or PCP. This hyperactivity was sustained for more than 2 h. Following microinjection of these Ca antagonists into the caudate putamen, each showed a different pattern of inhibition on MAP- or PCP-induced abnormal behaviors. Nic and Flu were effective at reducing these abnormal behaviors, in contrast, Nif was ineffective. In particular, the inhibitory effect of Nic was stronger than that of Flu. Microinjection of these Ca antagonists into the amygdala did not show any reductive effect on the hyperactivity induced by MAP or PCP. These results demonstrate that these Ca antagonists have different pharmacological properties and that both L- and T-type Ca2+ channels modulate the dopamine release in the rat caudate putamen. These results further lead us to suggest the presence of a subtype of L-type Ca2+ channels in the caudate putamen.
Hori
Y
Y
Department of Pharmacology, Tokyo Medical College, Japan.
Takeda
H
H
Tsuji
M
M
Matsumiya
T
T
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors*; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors*; D005444:Flunarizine / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors*; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009529:Nicardipine / Q000008:administration & dosage / Q000494:pharmacology; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology; D010622:Phencyclidine / Q000037:antagonists & inhibitors*; D011699:Putamen / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D008694:Methamphetamine; D009529:Nicardipine; D009543:Nifedipine; D010622:Phencyclidine; D005444:Flunarizine