Increase in the effectiveness of somatodendritic 5-HT-1A receptors in a rat model of tardive dyskinesia.
The present study concerns responsiveness of pre- and postsynaptic 5-hydroxytryptamine (5-HT)-1A receptors in a rat model of tardive dyskinesia (TD). Vacuous chewing movements (VCMs) in rats are widely accepted as an animal model of TD. Results show that haloperidol injected at a dose of 1 mg/kg twice a day for 5 weeks elicited VCMs, which increased in a time dependent manner following the drug administration for 3-5 weeks. Tolerance was produced in motor coordination during the potentiation of VCMs. Exploratory activity in an open field and in an activity box decreased in haloperidol treated animals. The effects of 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT; 0.5 mg/kg) were monitored 48-h after withdrawal from repeated administration of haloperidol. 8-OH-DPAT-induced locomotion was greater in haloperidol treated rats. 5-HT synthesis increased in haloperidol treated animals, while 8-OH-DPAT-induced decreases of 5-HT synthesis were greater in repeated haloperidol than repeated saline injected animals. The results suggest that an increase in the effectiveness of somatodendritic 5-HT-1A receptors may decrease the inhibitory influence of 5-HT on the activity of dopaminergic neurons to precipitate VCMs. The 5-HT-1A agonist may help to alleviate neuroleptic-induced TD.
Samad
Noreen
N
Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Laboratory, University of Karachi, Karachi-75270, Pakistan. noreensamad_ku@yahoo.com.
Khan
Asma
A
Perveen
Tahira
T
Haider
Saida
S
Abdul Haleem
Muhammad
M
Haleem
Darakhshan Jabeen
DJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000633:toxicity; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D006220:Haloperidol / Q000633:toxicity; D008297:Male; D008409:Mastication / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D018492:Dopamine Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006220:Haloperidol