Effect of deep brain stimulation in rats selectively bred for reduced prepulse inhibition

Abstract

Background: Sensorimotor gating, measured as prepulse inhibition (PPI) of the acoustic startle reaction (ASR), is disturbed in certain neuropsychiatric disorders, such as schizophrenia, obsessive compulsive disorder, and Tourette's syndrome (TS). Deep brain stimulation (DBS) of the centromedian-parafascicular complex (CM-Pf), globus pallidus internus (in rats the entopeduncular nucleus - EPN), and the ventral striatum (in rats the nucleus accumbens - NAC) has been used for treatment in TS.

Objective: We tested whether DBS of these regions would alleviate breeding-induced low PPI in rats.

Methods: Rats with breeding-induced low and high PPI were bilaterally implanted with electrodes in the CM-Pf, the EPN, or the NAC. After two weeks, they were stimulated or sham stimulated for epochs of 6 days (in the EPN with a current of 20% below the individual threshold for stimulation-induced side effects, in the NAC or CM-Pf with 100 μA and 150 μA). On the 6th day the rats were tested for PPI of ASR.

Results: Stimulation in the CM-Pf with 150 μA significantly alleviated PPI, while NAC stimulation was less effective. In PPI low rats electrode implantation in the EPN already improved PPI, while subsequent stimulation had no additional effect. Startle reaction of PPI low rats was not affected by stimulation of either region.

Conclusion: The CM-Pf and the EPN are important for the modulation of sensorimotor gating in rats with breeding-induced low PPI. These rats may therefore be useful to further investigate the pathophysiological mechanisms of deficient sensorimotor gating and also mechanisms of action of DBS in these circumstances.

Keywords: Centromedian parafascicular nucleus; Entopeduncular nucleus; Globus pallidus internus; Sensorimotor gating; Tourette's syndrome.