Sex Differences in Dopamine D2 Receptor Modulation of Striatal Dopamine in mGluR5-mediated Repetitive Self-grooming Behavior in the BTBR T+tf/J Mouse Model for Autism
Abstract
The Autism spectrum disorder (ASD) is characterized by deficient reciprocal social communication and repetitive behavior with restricted interests (DSM-V). The BTBR T+tf/J inbred mouse model (BTBR), which shows putative face validity for autistic traits, has been used to evaluate potential treatments for key symptoms of the disorder. Previous research has shown that Methyl-6-phenylethynyl-pyridine (MPEP), a selective mGluR5 antagonist, reduces the frequency of repetitive behavior, supporting the potential use of MPEP as a behavioral-modification treatment for ASD. MPEP has also been shown to upregulate dopaminergic transmission in the nucleus accumbens, limbic system and the basal ganglia. While the dopaminergic D1 and D2 receptors have been implicated in the modulation of restricted and repetitive behaviors (RRBs), not much research has been done on the interaction between mGluR5 and these receptors in the reduction of repetitive self-grooming behavior in BTBR.
This study was aimed at comparing the effects of MPEP treatment and dopamine D1 and D2 receptor antagonism on both the frequency and duration of self-grooming behavior in BTBR. We postulated that 1.0 mg/kg MPEP administration in combination with small doses of SCH22390 (a D1 antagonist) and Haloperidol (a D2 antagonist) would attenuate the reduction of repetitive self-grooming in BTBR by MPEP. The results obtained showed no significant effect of MPEP treatment on repetitive self-grooming which may be due to the combination of sample size and injection protocol used. We also observed increased repetitive behavior in female BTBR mice treated with 0.06 mg/kg Haloperidol. Our results show that sex differences may play a significant role in the pharmacological modulation of repetitive self-grooming behavior in BTBR mice.