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Locomotor activating effects of cocaine and scopolamine combinations in rats: isobolographic analysis

Thomsen, Morgane

doi: 10.1097/FBP.0000000000000043
Research Reports

Muscarinic cholinergic receptors are currently receiving renewed interest as viable targets for treating various psychiatric disorders. Dopaminergic and muscarinic systems interact in complex ways. The goal of this study was to quantify the interaction between a systemically administered psychomotor stimulant and muscarinic antagonist at the behavioral level. Through isobolographic analysis of locomotor activity data, we assessed the effects of three cocaine/scopolamine mixtures in terms of deviation from simple dose addition (additivity), at four effect levels. All three mixtures produced some more-than-additive (synergistic) effects, as lower doses were needed to produce the given effects relative to the calculated effect of additive doses. A mixture with comparable contributions from cocaine and scopolamine produced significantly more-than-additive effects at all but the lowest effect level examined. A mostly-cocaine mixture was more-than-additive only at low effect levels, whereas a mostly-scopolamine mixture produced effects more consistent with additivity, with only the highest effect level barely reaching significant synergism. Our study confirms and quantifies previous findings that suggested synergistic effects of stimulants and muscarinic antagonists. The synergism implies that cocaine and scopolamine stimulate locomotor activity through nonidentical pathways, and was most pronounced for a mixture containing cocaine and scopolamine in comparable proportions.

Alcohol and Drug Abuse Research Center, McLean Hospital/Harvard Medical School, Belmont, Massachusetts, USA

Correspondence to Morgane Thomsen, PhD, Alcohol and Drug Abuse Research Center, Harvard Medical School and McLean Hospital, Mail Stop 214, 115 Mill Street, Belmont, MA 02478, USA E-mail:

Received January 14, 2014

Accepted March 20, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins