Effects of haloperidol and risperidone on neurotensin levels in brain regions and neurotensin efflux in the ventral striatum of the rat.
Neurotensin (NT) may play a role in the pathophysiology of schizophrenia and in the mechanism of action of antipsychotic drugs. Here we studied the effects of a 30-day regimen of haloperidol (1.15 mg/100 g food) and risperidone (1.15 and 2.3 mg/100 g food) on NT-like immunoreactivity (-LI) levels in brain tissue and NT-LI efflux in the ventral striatum (VSTR) of the rat. Haloperidol, but not risperidone, increased NT-LI levels in the striatum. In the occipital cortex, risperidone, but not haloperidol, decreased levels of NT-LI. In the hippocampus and the frontal cortex both haloperidol and risperidone (the higher dose) increased NT-LI levels. In the VSTR, haloperidol and risperidone (the higher dose) decreased NT-LI efflux and abolished the stimulatory effect of d-amphetamine (1.5 mg/kg, s.c.). Thus, changes in NT occur in response to antipsychotic drugs and psychostimulants that may be relevant for the pathophysiology and treatment of schizophrenia.
Gruber
Susanne H M
SH
Institution of Clinical Neuroscience, Karolinska Institutet, St. Görans Hospital, S-112 81 Stockholm, Sweden.
Nomikos
George G
GG
Mathé
Aleksander A
AA
D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D015314:Dialysis Solutions / Q000378:metabolism; D006220:Haloperidol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009496:Neurotensin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D014018:Tissue Distribution / Q000187:drug effects
D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D015314:Dialysis Solutions; D009496:Neurotensin; D006220:Haloperidol; D018967:Risperidone; D003913:Dextroamphetamine