Systemic administration of dynorphin A(1-13) markedly inhibits different behavioural responses induced by cocaine in the mouse.
The effects of systemic administration (i.p.) of dynorphin A(1-13) on the cocaine-induced behavioural alterations in the mouse were determined by using multi-dimensional behavioural analyses, based upon a capacitance system. A 1.0 mg/kg dose of cocaine did not influence behaviour, while increasing doses to 3-30 mg/kg produced a significant increment in the frequency of behaviour, such as linear locomotion, circling, rearing and grooming. Although a 1.0 mg/kg dose of dynorphin A(1-13) alone produced a significant decrease in grooming behaviour, larger doses (3.0 and 10.0 mg/kg) of the peptide failed to affect different behaviour. The cocaine (3.0 mg/kg)-induced increases in linear locomotion, circling and rearing behaviour were significantly inhibited by dynorphin A(1-13) (10.0 mg/kg). The inhibitory effects of dynorphin A(1-13) (10.0 mg/kg) were antagonized by the opioid antagonist Mr 2266 (5.6 mg/kg). It is thus possible that the systemic administration of dynorphin A(1-13) inhibits different behavioural responses induced by cocaine through the blood-brain barrier, although the instability of amino acid bonds or the relatively large molecular weight of dynorphin A(1-13), may result in the failure to demonstrate opioid activity by the peptide after systemic administration.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
M
M
Ukai
T
T
Kamiya
T
T
Toyoshi
T
T
Kameyama
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001575:Benzomorphans / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009292:Narcotic Antagonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D000700:Analgesics; D001575:Benzomorphans; D009292:Narcotic Antagonists; D010446:Peptide Fragments; C027247:MR 2266; C026843:dynorphin (1-13); D004399:Dynorphins; D003042:Cocaine