RATIONALE: 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. OBJECTIVES: 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.
RATIONALE: 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. OBJECTIVES: 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.
Authors: Alexander G Zestos; Colleen Carpenter; Youngsoo Kim; Malcolm J Low; Robert T Kennedy; Margaret E Gnegy Journal: ACS Chem Neurosci Date: 2018-11-08 Impact factor: 4.418
Authors: Jonathan S Miller; Jeffrey L Barr; Lauren J Harper; Rachel L Poole; Thomas J Gould; Ellen M Unterwald Journal: PLoS One Date: 2014-02-04 Impact factor: 3.240