title: Effects of highly selective kappa-opioid agonists on EEG power spectra and behavioural correlates in conscious rats.
abstract: The present study compares the electroencephalographic (EEG) and behavioural effects of highly selective kappa-opioid agonists, spiradoline (U62066), enadoline (CI-977), BRL 52656, and BRL 53001, after SC administration to conscious rats. All compounds caused a distinctive dose- and time-related EEG effect and behavioural profile. The EEG power spectra (PS) of treated animals were characterised by power reduction indicative of CNS activation and an unusual spectral peak at 4-7 Hz, compared to controls. Behaviourally, however, the animals appeared to be sedated, with a reduction of locomotor activity, loss of postural tone, ataxia, and unusual hyperreactivity. The compounds differed in their liability to produce these CNS effects, with kappa-opioid analgesics such as enadoline and BRL 53001 showing a reduced propensity at equivalent antinociceptive doses. Where tested, these effects were inhibited by the nonselective opioid antagonist naloxone. The non-brain penetrating kappa-opioid agonist, BRL 52974, failed to produce alterations in EEG PS or behaviour, up to a dose of 10 mg/kg, indicating that the effects depend on activation of centrally located kappa-receptors.
authors.affiliation: Department of Biology, SmithKline Beecham Farmaceutici, Baranzate, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Coltro Campi
authors.forename: G D
authors.initials: GD
authors.lastname: Clarke
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects*; D005583:Fourier Analysis; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D011187:Posture / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D012890:Sleep / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
chemical_list: D017473:Receptors, Opioid, kappa; D009270:Naloxone