Locomotor activity and antinociception after putative mu, kappa and sigma opioid receptor agonists in the rat: influence of dopaminergic agonists and antagonists
Journal of Pharmacology and Experimental Therapeutics 217(2): 451-460
ISSN/ISBN: 0022-3565 PMID: 6262485 Accession: 005826304
The antinociceptive responses of 3 opioid agonists were compared to their effects of spontaneous locomotor activity in rats. Horizontal locomotor activity, performance on an accelerating rotarod and antinociception on the 49.5.degree. C hotplate were recorded after parenteral administration of putative mu, kappa and sigma opioid receptor agonists. The mu opioid agonist, morphine, produced analgesia and stimulated locomotion; the kappa opioid agonist, ketocyclazocine, produced analgesia and caused sedation/ataxia; and the sigma opioid agonist, SKF-10,047 (N-allylnormetazocine), stimulated locomotor activity but lacked antinociceptive effects. Naltrexone administration, 0.25-1 mg/kg, antagonized morphine- and ketocyclazocine-induced analgesia, and morphine-induced locomotion; a large dose of naltrexone (20 mg/kg) was required to diminish locomotion induced by SKF-10,047. Morphine- and SKF-10,047-induced locomotion were depressed after pretreatment with 0.03 mg/kg of spiperone (a putative dopamine receptor blocker) and by 0.1 mg/kg of apomorphine, which purportedly causes presynaptic inhibition of dopaminergic neurons. The depression by morphine- and SKF-10,047-induced locomotion produced by 0.1 mg/kg of apomorphine was reversed by a 0.01 mg/kg dose of spiperone. Morphine and ketocyclazocine analgesia was not appreciably altered by 0.1 mg/kg of apomorphine or 0.03 mg/kg of spiperone. SKF-10,047 antagonized both morphine and ketocyclazocine antinociception. Opioid-induced antinociception may be initiated by mu and kappa opioid-receptor interactions; opioid-induced hypermotility may originate from mu and sigma opioid-receptor interactions. The opioid-induced hypermotility may depend upon dopamine-containing mesostriatal and/or mesocorticolimbic systems, as opioid-induced locomotion was disrupted by both presynaptic and postsynaptic inhibitors of dopamine neurotransmission.