Evidence that the enhancement of dopamine function by repeated electroconvulsive shock requires concomitant activation of D1-like and D2-like dopamine receptors.
In this study, the behavioural response to dopamine D1-like receptor agonists (SKF 38393, SKF 81297 and SKF 77434) and D2-like receptor agonists (quinpirole and RU 24213), administered alone and in combination to rats treated repeatedly with electroconvulsive shock (five ECS over 10 days) or sham, was tested. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Repeated ECS (compared to sham controls) had no significant effect on the behavioural response to SKF 38393 (7.5 mg/kg s.c.), SKF 81297 (0.2 mg/kg s.c.), SKF 77434 (0.1 mg/kg s.c.), quinpirole (0.1 and 0.25 mg/kg s.c.) or RU 24213 (0.3 mg/kg s.c.), when administered alone. In contrast, repeated ECS markedly increased locomotion (activity counts and scores) induced by the non-selective dopamine agonist apomorphine (0.5 mg/kg SC) and by co-administration of a D1-like agonist plus a D2-like agonist [SKF 38393 (7.5 mg/kg s.c.) plus quinpirole (0.25 mg/kg s.c.), SKF 81297 (0.2 mg/kg s.c.) plus quinpirole (0.1 mg/kg s.c), and SKF 77434 (0.1 mg/kg s.c.) plus RU 24213 (0.3 mg/kg s.c.)]. This ECS-induced enhancement of dopamine-mediated behaviour was observed for up to 3 weeks after cessation of ECS treatment. In addition, ECS also enhanced the locomotor response to intra-accumbens SKF 38393 plus quinpirole (0.4 and 1.0 microgram/side, respectively). These results provide evidence that the enhancement of dopamine function by repeated ECS requires concomitant stimulation of both D1-like and D2-like receptors, and that this effect is long-lasting.
Smith
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University of Oxford, Department of Clinical Pharmacology, Radcliffe Infirmary, UK. stephen.smith@wadham.ox.ac.uk
Sharp
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D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology*; D004597:Electroshock; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2