Repeated co-administration of caffeine and bromocriptine prevents tolerance to the effects of caffeine in the turning behavior animal model.
The present study examined the effects of repeated co-administrations of caffeine and bromocriptine for 9 consecutive days on contralateral turning in unilateral nigrostriatal 6-hydroxydopamine denervated rats. In agreement with previous data, our results showed that on the first administration, both caffeine and bromocriptine injected plus saline produced a significant increase in contralateral rotational behavior as compared to saline-saline injections. However, with repeated administrations, tolerance was observed to caffeine, but not to bromocriptine. The combination of different doses of bromocriptine (0.1, 0.2, 0.4 and 0.8 mg/kg) with caffeine (40 mg/kg) significantly enhanced the effects of either drug injected with saline on rotational behavior, and no tolerance was observed with repeated treatment. The continuous co-administration of both substances was necessary to maintain elevated levels of rotational behavior, since withdrawing one or the other drug led to decreased contralateral turning. These results demonstrate that when caffeine is administered repeatedly in combination with bromocriptine, tolerance to its psychostimulant effects is not observed, suggesting that caffeine could be used as an adjunctive therapeutic agent with dopamine agonists for the treatment of Parkinson's disease.
Casas
M
M
Departament de Psiquiatria, Institut de Recerca Sant Pau, Programa Sant Pau-CITRAN y FISP, Universitat Autònoma de Barcelona, Unitat de Toxicomanies, Hospital de la Sta. Creu i St. Pau, Barcelona, Spain. 1574@hsp.santpau.es
Prat
G
G
Robledo
P
P
Barbanoj
M
M
Kulisevsky
J
J
Jané
F
F
D018663:Adrenergic Agents; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D008297:Male; D008474:Medial Forebrain Bundle / Q000293:injuries; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats
D018663:Adrenergic Agents; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D001971:Bromocriptine; D002110:Caffeine; D016627:Oxidopamine