Cocaine and caffeine elicit different dopamine receptor-mediated locomotor activity profiles: insights from a new model

Background The locomotor activity elicited by cocaine and caffeine can be distinguished via their underlying mechanisms and via differential responses to neuropharmacological manipulations. However, both cocaine- and caffeine-induced locomotor activity can be blocked by non-selective dopamine receptor antagonists, implying that we may not be able to distinguish their locomotor activity at the level of the dopamine receptor-mediated mechanism. With the rationale that this limitation may be due to a lack of sensitivity of current methods, we have developed a new Quantitative Structure of Curve Analytical (QSCAn) model. We hypothesized that QSCAn will be more effective, relative to the current model, in differentiating the dopamine receptor-mediated mechanism of cocaine versus caffeine-induced locomotor activity. Methods We assessed locomotor activity (quantified as distance traveled in cm over time) due to injections of saline (n = 6), cocaine (10 mg/kg i.p, n = 8) and caffeine (20 mg/kg i.p, n = 6) in male Sprague Dawley rats with and without pretreatment with vehicle and cis-flupenthixol (0.2 mg/kg i.p, non-selective dopamine receptor blocker)(current model). Because distance traveled over time follows an inverted u-shaped time-response curve, we employed gaussian fit of this structure to obtain several behavioral variables (QSCAn model). We compared both models. Results The current model could not distinguish the locomotor activity profile of cocaine versus caffeine following vehicle and cis-flupenthixol pretreatments. QSCAn model could distinguish cocaine versus caffeine in the presence and absence of non-selective dopamine receptor blockade. Conclusions The new QSCAn model may be a promising tool to distinguish/characterize different psychostimulant-related effects.