Selective activation of D1 dopamine receptors impairs sensorimotor gating in Long-Evans rats

Sensorimotor gating is a perceptual process aimed at filtering out irrelevant information. In humans and animal models, this function can be operationally measured through the prepulse inhibition (PPI) of the acoustic startle reflex. Notably, PPI deficits are associated with numerous neuropsychiatric conditions characterized by gating disturbances, including schizophrenia and Tourette syndrome. Ample evidence has shown that dopamine plays a key role in PPI regulation and, in particular, rodent studies indicate that this neurotransmitter modulates PPI through D1 and D2 dopamine receptors. In mice, the relative contributions of these two families of receptors are strain-dependent. Conversely, the role of D1 receptors in the regulation of PPI across different rat strains remains unclear.

We tested the effects of selective D1 and D2 receptor agonists and antagonists on the startle reflex and PPI of Sprague-Dawley, Wistar and Long-Evans rats.

In contrast with Sprague-Dawley and Wistar rats, the full D1 receptor agonist SKF82958 elicited significant PPI deficits in Long-Evans rats, an effect sensitive to the selective D1 antagonist SCH23390.

Our results suggest that, in Long-Evans rats, D1 receptor activation may be sufficient to significantly impair PPI. These data emphasize the role of D1 receptors in the pathophysiology of neuropsychiatric disorders featuring alterations in sensorimotor gating, and uphold the importance of the genetic background in shaping the role of dopamine receptors in the regulation of this key information-processing function.

This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc.