In vivo microdialysis studies of striatal level of neurotransmitters after haloperidol and chlorpromazine administration.
Therapeutic success of atypical antipsychotics has focused the attention on the role of receptor systems other than dopaminergic system in the pathophysiology of neuroleptics-associated acute (Parkinson's like syndrome) and chronic (tardive dyskinesia) extrapyramidal side effects. This study was planned to investigate changes in striatal levels of norepinephrine, dopamine and serotonin after acute and chronic administration of classical neuroleptics (haloperidol and chlorpromazine). These changes were correlated with behavioural alterations in rats. In vivo microdialysis with HPLC/ECD system revealed that there was a marked decrease in striatal neurotransmitter contents (NE, DA and 5-HT), which was also correlated with severe cataleptic response in rats after acute administration of haloperidol (2 mg/kg) and chlorpromazine (20 mg/kg). Chronic administration of haloperidol (1 mg/kg for 21 days) and chlorpromazine (5 mg/kg for 21 days) resulted in time dependent increase in orofacial hyperkinetic movements. The microdialysis studies also showed a significant decrease in the striatal levels of all the neurotransmitters. The results provide evidence for the involvement of striatal adrenergic and serotonergic systems, besides dopaminergic system in neuroleptic-induced acute and chronic extrapyramidal symptoms.
Centre with Potential for Excellence in Biomedical Sciences (CPEBS), Panjab University, Chandigarh 160 014, India. skpu@yahoo.com
Shrinivas K
SK
Kulkarni
Mahendra
M
Bishnoi
Kanwaljit
K
Chopra
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001479:Basal Ganglia / Q000737:chemistry* / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D002746:Chlorpromazine / Q000009:adverse effects / Q000494:pharmacology*; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects*; D004298:Dopamine / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D006220:Haloperidol / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000032:analysis*; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000032:analysis
D014150:Antipsychotic Agents; D018377:Neurotransmitter Agents; D012701:Serotonin; D006220:Haloperidol; D002746:Chlorpromazine; D004298:Dopamine; D009638:Norepinephrine