EFFECTS OF HIGHLY SELECTIVE KAPPA-OPIOID AGONISTS ON EEG POWER SPECTRA AND BEHAVIORAL-CORRELATES IN CONSCIOUS RATS

The present study compares the electroencephalographic (EEG) and behav ioural effects of highly selective kappa-opioid agonists, spiradoline (U62066), enadoline (CI-977), BRL 52656, and BRL 53001, after SC admin istration to conscious rats. All compounds caused a distinctive dose- and time-related EEG effect and behavioural profile. The EEG power spe ctra (PS) of treated animals were characterised by power reduction ind icative of CNS activation and an unusual spectral peak at 4-7 Hz, comp ared to controls. Behaviourally, however, the animals appeared to be s edated, 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 s uch as enadoline and BRL 53001 showing a reduced propensity at equival ent antinociceptive doses. Where tested, these effects were inhibited by the nonselective opioid antagonist naloxone. The non-brain penetrat ing 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 eff ects depend on activation of centrally located kappa-receptors.