gms | German Medical Science

Objective: Here we investigated whether deep brain stimulation (DBS) of the rat centromedian-parafascicular complex (CM-Pf) improves deficient sensorimotor gating induced by either the dopamine-receptor agonist apomorphine, or the NMDA-receptor antagonist dizocilpine. Deficient sensorimotor gating, measured as reduced prepulse inhibition (PPI) of the acoustic startle response, has been shown in the subset of neuropsychiatric disorders, such as schizophrenia and Tourette's syndrome among others. PPI-deficits induced by apomorphine or dizocilpine in rats have been used as endophenotypes for certain symptoms in these disorders. We recently showed that stimulation of the CM-Pf, a target for DBS in Tourette's syndrome, improves breeding-induced deficient sensorimotor gating.

Method: Using stereotaxy, electrodes were implanted bilaterally in the CM-Pf of Sprague Dawley rats. After recovery from surgery, the rats were stimulated with 150 μA (130 Hz and 160 μs square wave pulse) or sham stimulated (without any current) for epochs of five days via a cable connected to the stimulator device. The effects of DBS on apomorphine- (vehicle and 1.0 mg/kg) or dizocilpine- (vehicle and 0.15 mg/kg) induced deficient PPI were tested on the last day of each stimulation epoch. Finally, the location of the electrodes was histologically verified.

Results: CM-Pf DBS prevented the apomorphine-induced PPI-deficit, while dizocilpine-induced reduced PPI was not affected. In vehicle-treated rats DBS had no effect on PPI.

Conclusions: This work indicates an important role of the CM-Pf for the modulation of sensorimotor gating by the dopamine transmitter system, while the glutamatergic transmitter system seems to be less involved. This model may also be used to further investigate the mechanisms of action of DBS in certain neuropsychiatric disorders.