The effects of chronic administration of quetiapine on the methamphetamine-induced recognition memory impairment and dopaminergic terminal deficit in rats.
Previous studies have suggested that quetiapine, a new atypical antipsychotic drug, may have beneficial effects on cognitive impairment and be a neuroprotectant in treating neurodegenerative diseases. In the present study, we investigated the therapeutic effects of chronic administration of quetiapine on methamphetamine (METH)-induced recognition memory impairment and dopaminergic terminal neurotoxicity in rats. Rats were pretreated with METH (5 mg/kg; s.c.) four times at 2-h intervals while their body temperature was monitored. Fifteen minutes after the last METH injection, rats were administered quetiapine (10 mg/kg/day; i.p.) for 28 days. One day after the last quetiapine injection, rats were trained and tested on an object recognition task on days 29 and 30. Finally, on day 31, rats were sacrificed for immunohistochemistry, 1 day after the object recognition task. METH induced hyperthermia, recognition memory impairment and a decrease of tyrosine hydroxylase immunoreactivity in the caudate putamen (CPu) of striatum. Quetiapine attenuated the METH-induced hyperthermia. Furthermore, chronic post-treatment of quetiapine reversed the METH-induced memory impairment and dopaminergic terminal deficit. These findings suggest that quetiapine may have therapeutic effects in the treatment of cognitive impairment and neurodegeneration induced by METH.
He
Jue
J
Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, 103 Wiggins Road, Saskatoon, Sask., Canada S7N 5E4.
Yang
Yi
Y
Yu
Yingxin
Y
Li
Xiaokun
X
Li
Xin-Min
XM
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers; D001831:Body Temperature / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D005106:Exploratory Behavior / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced* / Q000523:psychology*; D008694:Methamphetamine / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D000069348:Quetiapine Fumarate; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014150:Antipsychotic Agents; D015415:Biomarkers; D000697:Central Nervous System Stimulants; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine