Behavioural effects of selective mu-, kappa-, and delta-opioid agonists in neonatal rats

The behavioural effects of selective mu-, kappa- and delta-opioid agonists in 5-, 10- and 20-day-old rats were investigated by observational analysis. The predominant response to mu-agonists was behavioural depression. High doses (10 mg/kg IP) of morphine and DAGO (D-Ala2, NMe-Phe4, Glyol5-enkephalin) produced overt sedation in all the age groups and also induced catalepsy which was particularly apparent in the 5- and 10-day-old animals. These compounds did not produce any signs of behavioural activation in the neonatal rats. In contrast, rat pups treated with the kappa-agonists U50,488H and PD 117,302 (1,10 mg/kg IP) exhibited marked hyperactivity with increases in wall-climbing and locomotion. Sedative effects of the highest dose of the kappa-agonists began to emerge, however, as the animals grew older, resulting in significant decreases in behaviours such as gnawing and grooming at 20 days of age. The kappa-agonist (+)-tifluadom (0.1-10 mg/kg), but not its corresponding (-)-isomer, produced an increase in activity in 5-day-old rats, thus extending the observations made with U50,488H and PD 117,302 and establishing the stereoselective nature of the response. The involvement of kappa-receptors in opioid-induced hyperactivity was further substantiated by using a variety of opioid antagonists. In this context, the increase in activity induced by U50,488H (10 mg/kg) in 5-day-old neonates was attenuated by naltrexone (1 mg/kg IP) but not by larger doses (10 mg/kg) of either M8008 (which has low affinity for kappa-receptors) or the selective delta-receptor antagonist ICI 174,864.(ABSTRACT TRUNCATED AT 250 WORDS)