Haloperidol but not clozapine increases neurotensin receptor mRNA levels in rat substantia nigra.
We examined the effects of chronic (2 weeks) treatment with a typical neuroleptic, haloperidol (1 mg/kg, s.c.), and an atypical neuroleptic, clozapine (20 mg/kg, s.c.), on neurotensin receptor (NTR) mRNA levels by in situ hybridization histochemistry. Quantitative OD analysis showed haloperidol-induced NTR mRNA levels in the substantia nigra/ventral tegmental area (SN/VTA) 110% over control levels (significant difference from the control, p < 0.05). In contrast, the same analysis applied to the sections from clozapine-treated animals showed no significant change in NTR mRNA levels compared with matched control sections (p > 0.05). Thus, chronic treatment with haloperidol but not clozapine resulted in elevated levels of NTR mRNA within the SN/VTA. These results suggest that the high incidence of extrapyramidal side effects of typical neuroleptics could result from changes in NTR expression in the SN/VTA.
Department of Psychiatry and Psychology, Mayo Foundation and Clinic Jacksonville 32224.
C
C
Bolden-Watson
M A
MA
Watson
K D
KD
Murray
P J
PJ
Isackson
E
E
Richelson
D000818:Animals; D001483:Base Sequence; D003024:Clozapine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter / Q000235:genetics*; D013378:Substantia Nigra / Q000378:metabolism*
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter; D003024:Clozapine; D006220:Haloperidol