title: Continuous stimulation of the pedunculopontine tegmental nucleus at 40 Hz affects preparative and executive control in a delayed sensorimotor task and reduces rotational movements induced by apomorphine in the 6-OHDA parkinsonian rat.
abstract: The pedunculopontine tegmental nucleus (PPTg) relays basal ganglia signals to the thalamus, lower brainstem and spinal cord. Using the 6-hydroxydopamine (6-OHDA) rat model of parkinsonism, we investigated whether deep brain stimulation (DBS) of the PPTg (40 Hz, 60 μs, 200-400 μA) may influence the preparative and executive phases in a conditioned behavioural task, and the motor asymmetries induced by apomorphine. In the conditioned task, rats had to press two levers according to a fixed delay paradigm. The 6-OHDA lesion was placed in the right medial forebrain bundle, i.e. contralaterally to the preferred forepaw used by rats to press levers in the adopted task. The stimulating electrode was implanted in the right PPTg, i.e. contralateral to left side, which was expected to be most affected. The lesion significantly reduced correct responses from 63.4% to 16.6%. PPTg-DBS effects were episodic; however, when rats successfully performed in the task (18.9%), reaction time (468.8 ± 36.5 ms) was significantly increased (589.9 ± 45.9 ms), but not improved by PPTg-DBS (646.7 ± 33.8 ms). Movement time was significantly increased following the lesion (649.2 ± 42.6 ms vs. 810.9 ± 53.0 ms), but significantly reduced by PPTg-DBS (820.4 ± 39.4 ms) compared to sham PPTg-DBS (979.8 ± 47.6 ms). In a second group of lesioned rats, rotations induced by apomorphine were significantly reduced by PPTg-DBS compared to sham PPTg-DBS (12.2 ± 0.6 vs. 9.5 ± 0.4 mean turns/min). Thus, it appears that specific aspects of motor deficits in 6-OHDA-lesioned rats may be modulated by PPTg-DBS.
authors: Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, Via Vetoio, Coppito 2, I-67100 L'Aquila, Italy.
authors: Annamaria
authors: A
authors: Capozzo
authors: Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, Via Vetoio, Coppito 2, I-67100 L'Aquila, Italy.
authors: Flora
authors: F
authors: Vitale
authors: Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, Via Vetoio, Coppito 2, I-67100 L'Aquila, Italy.
authors: Claudia
authors: C
authors: Mattei
authors: Unit of Functional Neurosurgery, CTO Alesini Hospital ASL Rome C, Via San Nemesio 21, 00145 Rome, Italy.
authors: Paolo
authors: P
authors: Mazzone
authors: Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, Via Vetoio, Coppito 2, I-67100 L'Aquila, Italy. Electronic address: scarnati@univaq.it.
authors: Eugenio
authors: E
authors: Scarnati
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D056344:Executive Function; D008297:Male; D009068:Movement; D016627:Oxidopamine / Q000506:poisoning; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D045042:Pedunculopontine Tegmental Nucleus / Q000503:physiopathology*; D011597:Psychomotor Performance; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D016896:Treatment Outcome
chemical_list: D018491:Dopamine Agonists; D016627:Oxidopamine; D001058:Apomorphine
keywords: 6-Hydroxydopamine; Conditioned movement; Deep brain stimulation; Pedunculopontine tegmental nucleus; Rotational behavior