Ability of dopamine antagonists to inhibit the locomotor effects of cocaine in sensitized and non-sensitized C57BL/6 mice depends on the challenge dose

Eric P M Prinssen, Francis C. Colpaert, Mark S. Kleven, Wouter Koek

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Rationale: Studies in rats examining the ability of selective dopamine D2 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 D2 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 D2 class antagonists attenuated the locomotor effects of cocaine in sensitized and non-sensitized animals with similar potencies. The ability of the D1 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.

Original languageEnglish (US)
Pages (from-to)409-414
Number of pages6
JournalPsychopharmacology
Volume172
Issue number4
DOIs
StatePublished - Apr 2004

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Dopamine Antagonists
Inbred C57BL Mouse
Cocaine
Locomotion
eticlopride
Raclopride

Keywords

  • Antipsychotics
  • Behavioral sensitization
  • Cocaine
  • Dopamine D receptors
  • Dopamine D receptors
  • Locomotion
  • Neuroleptics

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ability of dopamine antagonists to inhibit the locomotor effects of cocaine in sensitized and non-sensitized C57BL/6 mice depends on the challenge dose. / Prinssen, Eric P M; Colpaert, Francis C.; Kleven, Mark S.; Koek, Wouter.

In: Psychopharmacology, Vol. 172, No. 4, 04.2004, p. 409-414.

Research output: Contribution to journalArticle

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abstract = "Rationale: Studies in rats examining the ability of selective dopamine D2 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 D2 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 D2 class antagonists attenuated the locomotor effects of cocaine in sensitized and non-sensitized animals with similar potencies. The ability of the D1 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.",
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