Ability of dopamine antagonists to inhibit the locomotor effects of cocaine in sensitized and non-sensitized C57BL/6 mice depends on the challenge dose.
BACKGROUND
Studies in rats examining the ability of selective dopamine D(2) receptor class antagonists to attenuate the effects of a cocaine challenge have suggested that these agents are less potent in attenuating sensitized as opposed to non-sensitized locomotion. A potential issue with these studies is that the same challenge dose is used in sensitized and control conditions even though that dose may occupy different positions on the respective dose-response curves.


OBJECTIVE
To examine whether the ability of dopamine antagonists to attenuate cocaine-induced locomotion differs between sensitized and non-sensitized animals if they are challenged with the same dose of cocaine, and with the lowest dose to maximally increase locomotion, which is lower in sensitized than in non-sensitized animals.


METHODS
Mice were treated repeatedly with 20 mg/kg cocaine or saline (for 3 consecutive days) and then challenged (after an 11-day drug-free interval) with different challenge doses of cocaine after pretreatment with a dopamine antagonist or saline.


RESULTS
Using the same challenge dose of cocaine in both repeated treatment conditions (i.e. 20 mg/kg), the D(2 )class antagonists eticlopride and raclopride were less potent in attenuating the locomotor effects of cocaine in sensitized than those in non-sensitized animals. In contrast, when the lowest doses to maximally increase locomotion in each of the repeated treatment conditions were used (10 and 40 mg/kg), the D(2 )class antagonists attenuated the locomotor effects of cocaine in sensitized and non-sensitized animals with similar potencies. The ability of the D(1) class antagonist SCH23390 to attenuate the effects of cocaine demonstrated a similar dependency on the challenge dose.


CONCLUSIONS
These results show that, under the present conditions, the ability of dopamine antagonists to attenuate cocaine-induced locomotion is similar in sensitized and non-sensitized animals when challenged with pharmacologically equivalent doses of cocaine, but not when challenged with the same dose.
Prinssen
Eric P M
EP
Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106 Castres Cedex, France.
Colpaert
Francis C
FC
Kleven
Mark S
MS
Koek
Wouter
W
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D020891:Raclopride / Q000494:pharmacology; D012457:Salicylamides / Q000494:pharmacology
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D012457:Salicylamides; D020891:Raclopride; D003042:Cocaine; C045989:eticlopride