Abstract:
Tardive dyskinesia is a serious and limiting side effect in long-term neuroleptic treatment that is still poorly understood. This study examined the expression of enkephalin (ENK), dynorphin (DYN), and D1 dopamine receptor (DRD1) mRNA, utilizing in situ hybridization histochemistry, in a cohort of rats chronically given haloperidol (HAL) decanoate (N=43) or control (N=21) injections for 24 weeks to determine if a relationship between striatal mRNA expression and vacuous chewing movements (VCMs) in two different noise conditions could be determined. Although HAL decanoate significantly increased ENK mRNA, this increase was not correlated with VCMs. Neither a significant HAL effect nor a correlation with VCMs was found for DRD1 mRNA. While HAL decanoate did not statistically significantly increase DYN mRNA in the experimental group, a statistically significantly positive correlation was found between DYN mRNA expression and VCM rates, but only when noises were present. These
results indicate that a significant change in the direct pathway contributes to the determination of VCM activity, but only in some of the rats treated with HAL, implicating individual variation in striatal DYN mRNA as playing a critical role in VCM activity, specifically in the exacerbation of VCMs by stress.
