The Partial M₁ Muscarinic Cholinergic Receptor Agonist, CDD-0102A, Differentially Modulates Glutamate Efflux in Striatal Subregions during Stereotyped Motor Behavior in the BTBR Mouse Model of Autism

The BTBR T+ Itpr3(tf)/J (BTBR) mousedisplayselevated repetitive motor behaviors. Treatment with the partial M-1 muscarinic receptor agonist, CDD-0102A, attenuates stereotypedmotor behaviors in BTBR mice. The present experiment investigatedwhether CDD-0102A modifies changes in striatal glutamate concentrationsduring stereotyped motor behavior in BTBR and B6 mice. Using glutamatebiosensors, change in striatal glutamate efflux was measured duringbouts of digging and grooming behavior with a 1 s time resolution.Mice displayed both decreases and increases in glutamate efflux duringsuch behaviors. Magnitude of changes in glutamate efflux (decreasesand increases) from dorsomedial and dorsolateral striatum were significantlygreater in BTBR mice compared to those of B6 mice. In BTBR mice, CDD-0102A(1.2 mg/kg) administered 30 min prior to testing significantly reducedthe magnitude change in glutamate decreases and increases from thedorsolateral striatum and decreased grooming behavior. Conversely,CDD-0102A treatment in B6 mice potentiated glutamate decreases andincreases in the dorsolateral striatum and elevated grooming behavior.The findings suggest that activation of M-1 muscarinic receptorsmodifies glutamate transmission in the dorsolateral striatum and self-groomingbehavior.