Priming of rotational behavior by a dopamine receptor agonist in Hemiparkinsonian rats: movement-dependent induction.
Repetitive stimulation of dopamine receptors located in the basal ganglia may lead to the manifestation of sensitized, abnormal, motor responses in dopamine-denervated rats. In order to study the role of motor behavior execution on the expression of these altered motor responses, we evaluated how "priming", a phenomenon displaying neurochemical and behavioral features peculiar to a sensitized abnormal motor response in dopamine-denervated rats, depends on actual movement performance. To this end, unilaterally 6-hydroxydopamine-lesioned rats received apomorphine (0.2 mg/kg s.c.), being either allowed to move or immobilized (1 h) before, concomitantly to, or after its administration, respectively. Three days after apomorphine, the dopamine D(1) receptor agonist 1-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393, 3 mg/kg s.c.) was administered to all animals. Rats that had performed rotational behavior following apomorphine administration displayed robust contraversive rotational behavior in response to SKF 38393, whereas rats that had been immobilized concomitantly to, but neither before nor after apomorphine, did not. To clarify whether stress, which may be increased by immobilization, mediated the results observed, additional rats received apomorphine paired with immobilization plus the corticosterone-synthesis inhibitor metyrapone (100 mg/kg i.p.), or apomorphine paired with a tail stressor, being not immobilized. Metyrapone did not affect the capacity of immobilization to prevent priming and tail stressor imposition did not affect priming magnitude, suggesting that stress has minimal or no effect on the results observed. This study demonstrates how movement performance following initial dopaminergic stimulation governs the occurrence of a sensitized, abnormal, motor response to a subsequent dopaminergic challenge in dopamine-denervated rats.
Simola
N
N
Department of Toxicology and Centre of Excellence for Neurobiology of Dependence, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy.
Di Chiara
G
G
Daniels
W M U
WM
Schallert
T
T
Morelli
M
M
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine; D018491:Dopamine Agonists / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D009068:Movement / Q000187:drug effects*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000379:methods; D045442:Rotarod Performance Test / Q000379:methods; D012399:Rotation; D013997:Time Factors
D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine; D008797:Metyrapone