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.