Dopamine 'D2-like' receptor agonists in combination with cocaine: absence of interactive effects on locomotor activity.
This study examined interactions between cocaine and drugs that act as direct agonists at subtypes of "D2-like" dopamine receptors. The drugs 7-OH-DPAT, quinpirole and RU24213 were studied alone and in combination with cocaine for their effects on locomotor activity in non-habituated mice. Locomotor activity was measured by photobeam crossings over 140 min. At the doses given (7-OH-DPAT: 0.006-6.4 mg/kg; quinpirole: 0.001-1 mg/kg; RU24213: 0.008-8 mg/kg) all three direct agonists dose-dependently reduced locomotor activity throughout the test, whereas cocaine (0.6-20 mg/kg) produced dose-related hyperactivity. Next, for each direct agonist, a series of doses was selected (up to threshold behaviourally-active doses) as pretreatments to a sub-maximally stimulant dose of cocaine (15 mg/kg). 7-OH-DPAT and quinpirole did not modulate the effects of cocaine; RU24213 produced, at best, a very modest attenuation of the effects of cocaine. Finally, a series of cocaine doses (below stimulant threshold) was given before a single dose of each direct agonist (the lowest dose to reduce activity significantly). Cocaine did not reliably alter the hypoactivity produced by any of the D2-like agonists. By demonstrating negligible interactions between cocaine and D2-like agonists, the results fail to demonstrate any necessary involvement of D2-like receptors in one of the behavioural effects of cocaine.
Tirelli
E
E
Unité de Psychologie Biologique et de Pharmacopsychology, Université de Liège au Campus du Sart-Tilman, Belgium.
Reggers
J
J
Terry
P
P
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D010627:Phenethylamines; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; D003042:Cocaine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin