Neurotoxin-induced lesions to central serotonergic, noradrenergic and dopaminergic systems modify caffeine-induced antinociception in the formalin test and locomotor stimulation in rats

Our study examined the effects of neurotoxin-induced lesions to central 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA) systems on antinociception by caffeine in the formalin test and on locomotor stimulation by caffeine. Locomotor activity was determined simultaneously with responses to formalin, although in some studies, scores were derived in the absence of formalin. Rats were tested 10 to 12 days after toxin administration, and amine levels in brain regions and the spinal cord determined at the end of the experiment. Intracerebroventricular 5,7-dihydroxytryptamine (+/- desipramine) (which depleted central 5-HT systems) inhibited antinociception by caffeine but had no effect on locomotor stimulation. Intracerebroventricular 6-hydroxydopamine (which depleted NA in brain and spinal cord and DA in brain) augmented both antinociception and locomotor stimulation by caffeine. Both effects were due to NA depletion as they were mimicked by microinjection of 6-hydroxydopamine into the locus ceruleus that selectively depleted NA, not by intracerebroventricular 6-hydroxydopamine with desipramine that selectively depleted DA. In the absence of formalin, locus ceruleus lesions no longer had a significant effect on locomotor stimulation. Phentolamine, an alpha-adrenergic antagonist, inhibited caffeine-induced locomotor stimulation in the absence of formalin. These neurotoxin-induced lesions reveal an involvement of central 5-HT and NA (but not DA) systems in antinociception, and an involvement of central NA (but not 5-HT or DA) systems in locomotor stimulation. There appears to be an interrelationship between noxious stimulation and the expression of locomotor activity.