Low-dose pretreatment with clorgyline decreases the levels of 3-methoxy-4-hydroxyphenylglycol in the striatum and nucleus accumbens and attenuates methamphetamine-induced conditioned place preference in rats.
The effect of treating rats with clorgyline, an irreversible monoamine oxidase-A (MAO-A) inhibitor, on methamphetamine (METH)-induced conditioned place preference (CPP) was investigated. Administering rats with METH (1.0 mg/kg i.p.) every other day during two conditioning sessions (i.e., saline/METH conditioning with no clorgyline pretreatment) induced a significant CPP compared with saline/saline conditioning. Pretreatment of the rats with clorgyline at a dose of 0.1 mg/kg (i.p.), but not 1.0 or 10 mg/kg, attenuated the METH-induced CPP. Neurochemical analysis using high-performance liquid chromatography revealed that the tissue levels of monoamines and their metabolites were not significantly affected by treatment with 0.1 mg/kg clorgyline except for the levels of 3-methoxy4-hydroxyphenylglycol (MHPG) in the striatum and nucleus accumbens (NAc). Clorgyline at doses of 1.0 or 10 mg/kg significantly affected the tissue levels of 3,4-dihydroxyphenylacetic acid, norepinephrine (NE), MHPG, and serotonin in the cerebral cortex and those of all monoamines and metabolites examined in the striatum and NAc. A significant decrease in the MHPG/NE ratio in the striatum and NAc was apparent in the rats pretreated with 0.1 mg/kg clorgyline. Overall, the present study demonstrated that low-dose clorgyline attenuated METH-induced CPP in rats.
Kitanaka
N
N
Department of Pharmacology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Kitanaka
J
J
Watabe
K
K
Takemura
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D003010:Clorgyline / Q000008:administration & dosage / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000697:Central Nervous System Stimulants; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D008694:Methamphetamine; D008734:Methoxyhydroxyphenylglycol; D003010:Clorgyline; D009638:Norepinephrine