Sub-chronic treatment with classical but not atypical antipsychotics produces morphological changes in rat nigro-striatal dopaminergic neurons directly related to "early onset" vacuous chewing.
In the present work, we investigated if an impairment of dopaminergic neurons after subchronic haloperidol treatment might be a possible physiopathologic substrate of the "early onset" vacuous chewing movements (VCMs) in rats. For this purpose, different antipsychotics were used to analyse a possible relationship between VCMs development and morphological alterations of tyrosine-hydroxylase-immunostained (TH-IM) neurons. Rats treated twice a day with haloperidol displayed a significant increase of VCMs that was both time- (2-4 weeks) and dose (0.1-1 mg/kg) dependent. Immunocytochemical analysis showed a shrinkage of TH-IM cell bodies in substantia nigra pars compacta and reticulata and a reduction of TH-immunostaining in the striatum of haloperidol treated rats with the arising of VCMs. No differences were observed in TH-IM neurons of ventral tegmental area and nucleus accumbens vs. control rats. The atypical antipsychotics risperidone (2 mg/kg, twice a day), amisulpride (20 mg/kg, twice a day) and clozapine (10 mg/kg, twice a day) did not produce any nigro-striatal morphological changes or VCMs. TH-IM nigro-striatal neuron morphological alterations and VCMs were still present after three days of withdrawal in rats treated for four weeks with haloperidol (1 mg/kg). Both the main morphological changes and the behavioural correlate disappeared after three weeks of withdrawal. These results suggest that haloperidol induces a morphological impairment of the dopaminergic nigro-striatal neurons which is directly associated with the arising, permanency and disappearance of VCMs in rats.
Marchese
Giorgio
G
Neuroscienze S.c.a.r.l., and B.B. Brodie Department of Neuroscience, University of Cagliari, Italy.
Casu
Maria Antonietta
MA
Bartholini
Francesco
F
Ruiu
Stefania
S
Saba
Pierluigi
P
Gessa
Gian Luigi
GL
Pani
Luca
L
D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D003024:Clozapine / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006220:Haloperidol / Q000633:toxicity*; D008297:Male; D008409:Mastication / Q000187:drug effects / Q000502:physiology; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D009434:Neural Pathways / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000633:toxicity; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000633:toxicity
D014150:Antipsychotic Agents; D013469:Sulpiride; D000077582:Amisulpride; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D004298:Dopamine