Comparative studies of the neuro-excitatory behavioural effects of morphine-3-glucuronide and dynorphin A(2-17) following spinal and supraspinal routes of administration.
Morphine-3-glucuronide (M3G) administered centrally produces dose-dependent neuro-excitatory behaviours in rodents via a predominantly non-opioid mechanism. The endogenous opioid peptide, dynorphin A (Dyn A) (1-17), is rapidly cleaved in vivo to the relatively more stable fragment Dyn A(2-17) which also produces excitatory behaviours in rodents via a non-opioid mechanism. This study investigated the possible contribution of Dyn A(2-17) to the neuro-excitatory behaviours evoked by supraspinally and spinally administered M3G in male Sprague-Dawley (SD) rats. Marked qualitative differences in behaviours were apparent following administration of M3G and Dyn A(2-17). Administration of 11 nmol i.c.v. doses of M3G produced intermittent myoclonic jerks, tonic-clonic convulsions, and ataxia, as well as postural changes, whereas i.c.v. Dyn A(2-17) at 15 nmol produced effects on body posture alone. Administration of 11 nmol i.t. doses of M3G produced intermittent explosive motor activity, and touch-evoked agitation, as well as postural changes, whereas i.t. Dyn A(2-17) at 15 nmol produced postural changes, touch-evoked agitation, and paralysis. Pre-treatment with Dyn A antiserum (200 microg) markedly attenuated total behavioural excitation following i.c.v. and i.t. administration of Dyn A(2-17) by approximately 94% and 78%, respectively. However, total behavioural excitation following i.c.v. and i.t. administration of M3G was less markedly attenuated (both approximately 27%) by pre-treatment with Dyn A antiserum, with reductions in tonic-clonic convulsions ( approximately 43%), explosive motor behaviour ( approximately 28%), and touch-evoked agitation ( approximately 22%). The present findings discount a major role for Dyn A in mediating the neuro-excitatory effects of M3G, although it may contribute to maintaining some individual neuro-excitatory behaviours.
Hemstapat
Kamondanai
K
The University of Queensland, School of Pharmacy, St Lucia Campus, Brisbane, Queensland, 4072, Australia.
Le
Loan
L
Edwards
Stephen R
SR
Smith
Maree T
MT
D000818:Animals; D019540:Area Under Curve; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D009022:Morphine Derivatives / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D010243:Paralysis / Q000139:chemically induced; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011187:Posture; D011595:Psychomotor Agitation / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000697:Central Nervous System Stimulants; D009022:Morphine Derivatives; D010446:Peptide Fragments; D004399:Dynorphins; C082245:dynorphin (2-17); C018108:morphine-3-glucuronide