Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats.

摘要: Antipsychotics are an important class of drugs for the management schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors present throughout brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements face limbs which there is little treatment. In this study, we investigated whether nicotine administration could reduce dyskinesia attenuates drug-induced movements. We used a well established model in rats injected with commonly haloperidol develop vacuous chewing (VCMs) that resemble human orofacial dyskinesias. Rats were first administered (minipump; 2 mg/kg per day). Two weeks later, they given (1 s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs ∼20% after 5 weeks, significant ∼60% decline 13 weeks. There was no worsening catalepsy. To understand molecular basis improvement, measured striatal transporter nicotinic acetylcholine (nAChRs). Both decreased α6β2* nAChRs (the asterisk indicates possible presence subunits receptor complex) when alone, further combined drug By contrast, alone increased, while α4β2* both vehicle haloperidol-treated rats. data suggest mechanisms than those directly linked underlie nicotine-mediated improvement The results may be useful improving associated use.