Effects of acute and subchronic d-amphetamine on ventral striatal concentrations of neurotensin and neuropeptide Y in rats treated with antipsychotic drugs.
We have reported that acute d-amphetamine increases extracellular concentrations (efflux) of neurotensin-like immunoreactivity (NT-LI) and neuropeptide Y-LI (NPY-LI) in the ventral striatum (VSTR) of freely moving rats, effects that are abolished by chronic administration of haloperidol and risperidone admixed to food pellets. In this study we further investigated the d-amphetamine effects on NT-LI and NPY-LI efflux in VSTR and their content in selected brain regions. Rats received haloperidol, risperidone or vehicle for 30days and saline or d-amphetamine either on days 22-29 and/or day 30. Seven day d-amphetamine administration decreased basal NT-LI and NPY-LI efflux in vehicle-treated rats; pretreatment with haloperidol counteracted these effects, while pretreatment with risperidone had effect only on NT-LI. Acute d-amphetamine after the seven day d-amphetamine increased NT-LI only. Pretreatment with haloperidol or risperidone abolished the effects of acute d-amphetamine on NT-LI and NPY-LI. Acute and seven day d-amphetamine increased NT-LI and NPY-LI contents in striatum; seven day d-amphetamine also increased NT-LI in frontal and occipital cortex and both NT-LI and NPY-LI in hippocampus. Our results suggest that NT and NPY are involved in both the pathophysiology and the therapeutics of schizophrenia.
Gruber
Susanne H M
SH
Institution of Clinical Neuroscience, Karolinska Institutet, SE-141 52, Huddinge, Sweden.
Nomikos
George G
GG
Mathé
Aleksander A
AA
D000661:Amphetamine / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004334:Drug Administration Schedule; D004347:Drug Interactions; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000097:blood / Q000494:pharmacology; D008297:Male; D017551:Microdialysis / Q000379:methods; D009478:Neuropeptide Y / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism*; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000097:blood / Q000494:pharmacology; D013997:Time Factors
D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D009478:Neuropeptide Y; D009496:Neurotensin; D000661:Amphetamine; D006220:Haloperidol; D018967:Risperidone