Supersensitivity of spinal dopaminergic receptors in rat after chronic haloperidol.
In order to examine the effect of chronic neuroleptics on spinal dopaminergic system, rats were treated with haloperidol (0.5 mg/kg IP) for 21 days and the monosynaptic mass reflex (MMR) as well as dopamine (DA) metabolism were investigated. MMR, recorded from ventral root L6 following supramaximal stimulation to ipsilateral dorsal root L6 in spinalized rats, were found to be unaffected following chronic haloperidol treatment when compared to control. Apomorphine (0.1 mg/kg IV) caused 10-20% depression of MMR in control animals which was augmented to 40-50% in chronically haloperidol-treated animals suggesting an upregulation of DA receptors in the spinal cord. DA content of lumbar region of the spinal cord was unaffected whereas its major metabolite, homovanillic acid, was significantly reduced in chronic haloperidol-treated animals. This decreased utilization of DA may compensate the upregulation of DA receptors to maintain the physiological homeostasis of the spinal dopaminergic system.
Maitra
K K
KK
Division of Pharmacology and Experimental Therapeutics, Indian Institute of Chemical Biology, Jadavpur, Calcutta.
Seth
P
P
Mohanakumar
K P
KP
Ganguly
D K
DK
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012023:Reflex, Monosynaptic / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*; D013997:Time Factors
D011954:Receptors, Dopamine; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid