Effects of intracerebroventricularly administered mu-, delta- and kappa-opioid agonists on locomotor activity of the guinea pig and the pharmacology of the locomotor response to U50,488H.
The effects of intracerebroventricular administration of morphine, the selective mu-agonist DAMGO, the delta-agonist DPDPE, the kappa-preferring peptide dynorphin A(1-13) and the kappa-agonist U50,488H on locomotor behaviour in the guinea pig were investigated. Morphine (total dose = 0.01, 0.1, 1, 10, 200 nmol), DAMGO and DPDPE (total dose = 0.1, 1, 10, 100 nmol of each) produced piloerection and sedation, indicating that the responses of guinea pigs to mu- and delta-opioid agonists differed from those of rats and mice. In contrast, U50,488H (total dose = 10, 100 nmol) and dynorphin A(1-13) (total dose = 100 nmol) produced increased locomotor activity which was attenuated by pretreatment with naloxone and norbinaltorphimine, thus confirming the involvement of kappa-opioid receptors. Furthermore, pretreatment with spantide, baclofen, muscimol, bicuculline, MK-801, raclopride and atropine also inhibited the U50,488H-induced locomotor activity, suggesting the involvement of GABA, dopamine, excitatory amino acids, substance P and acetylcholine in this response.
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Neuropharmacology Laboratory, Faculty of Medicine, University of Newcastle, N.S.W., Australia.
Chahl
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Brent
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PJ
Johnston
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PA
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004399:Dynorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010863:Piloerection / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology
D000700:Analgesics; D004745:Enkephalins; D006993:Hypnotics and Sedatives; D009294:Narcotics; D010446:Peptide Fragments; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-