Assessment of the ambulation-increasing effect of ketamine by coadministration with central-acting drugs in mice.
The coadministration of ketamine (12.5 mg/kg, but not 3.1 mg/kg, s.c.) with methamphetamine (2 mg/kg, s.c.), cocaine (10 mg/kg, s.c.), scopolamine (0.5 mg/kg, s.c.), caffeine (10 mg/kg, s.c.) and MK-801 (0.1 mg/kg, i.p.) significantly enhanced the ambulation-increasing effects. Furthermore, in the coadministration with morphine (10 mg/kg, s.c.) and GBR-12909 (10 mg/kg, i.p.), not only 12.5 mg/kg but also 3.1 mg/kg of ketamine produced a significant enhancement. On the other hand, the ambulation-increasing effect of ketamine (12.5 mg/kg, s.c.) was significantly suppressed by ceruletide (0.01 mg/kg, i.p.), alpha-methyl-p-tyrosine (100 and 300 mg/kg, i.p. x 2), nimodipine (1 and 3 mg/kg, i.p.), haloperidol (0.03 and 0.1 mg/kg, s.c.), a low dose of apomorphine (0.1 mg/kg, s.c.), physostigmine (0.1 mg/kg, s.c.) and N6-(L-2-phenylisopropyl)-adenosine (0.1 mg/kg, s.c.). However, imipramine (20 mg/kg, i.p.), 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (100 mg/kg, s.c.), a high dose of apomorphine (0.5 mg/kg), reserpine (0.3 and 1 mg/kg, s.c.), propranolol (0.3 and 1 mg/kg, s.c.), phenoxybenzamine (3 and 10 mg/kg, s.c.) and naloxone (0.3 and 1 mg/kg, s.c.) scarcely interacted with ketamine. These results suggest that ketamine increases the ambulatory activity in mice by facilitating dopamine release from a newly synthesized pool at the presynaptic level, which is affected by a calcium-dependent mechanism.
Uchihashi
Y
Y
Division for Behavior Analysis, Gunma University School of Medicine, Maebashi, Japan.
Kuribara
H
H
Tadokoro
S
S
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002108:Ceruletide / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D002491:Central Nervous System Agents; D002492:Central Nervous System Depressants; D008781:Methyltyrosines; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D002110:Caffeine; D008694:Methamphetamine; D009553:Nimodipine; D019805:alpha-Methyltyrosine; D007649:Ketamine; D016291:Dizocilpine Maleate; D009020:Morphine; D002108:Ceruletide; C043425:vanoxerine; D012601:Scopolamine; D003042:Cocaine