Monoamine systems in the discriminative effects of spiradoline, a kappa-opioid agonist

The results of studies on mice indicate that the antinociceptive effects of kappa-opioid agonists are due, in part, to activation of the 5-HT2 type of serotonin receptor. One objective of this study was to determine if the discriminative effects of spiradoline, a kappa-opioid agonist, are mediated by 5-HT2 receptors in rats also. A second objective was to confirm findings that dopamine receptor antagonists produce spiradoline-like discriminative effects (Ohno et al., 1992). Rats were trained to discriminate between spiradoline (3.0 mg/kg) and saline in a discrete-trial avoidance/escape procedure. In subsequent tests of stimulus generalization, the discriminative effects of spiradoline were not mimicked by fenfluramine (0.3-10 mg/kg) or fluoxetine (1.0-10 mg/kg), drugs that enhance serotonergically mediated neurotransmission, nor were they blocked by the 5-HT2 antagonists pirenperone (0.01-1.0 mg/kg) and ketanserin (0.1-10 mg/kg), or potentiated by fluoxetine pretreatment. Neither the dopamine receptor antagonists haloperidol (0.01-0.3 mg/kg) and sulpiride (3.0-100 mg/kg) nor the agonists apomorphine (0.03-0.3 mg/kg) and d-amphetamine (0.1-3.0 mg/kg) engendered spiradoline-like discriminative effects. These results demonstrate further the pharmacological specificity of the discriminative effects of spiradoline, but provide no evidence for mediation by serotonergic or dopaminergic systems.