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.
Holtzman
S G
SG
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322-3090.
Steinfels
G F
GF
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D015306:Biogenic Monoamines / Q000502:physiology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D018492:Dopamine Antagonists; D005277:Fenfluramine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D005795:Generalization, Stimulus / Q000187:drug effects; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
D000700:Analgesics; D015306:Biogenic Monoamines; D018492:Dopamine Antagonists; D005277:Fenfluramine; D005473:Fluoxetine; D007650:Ketanserin; D010880:Piperidines; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C051272:spiradoline; C034177:pirenperone