Behavioural effects of selective ?-, ?-, and ?-opioid agonists in neonatal rats

Abstract

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)

U50, 488 increases ultrasonic vocalizations in 3‐, 10‐, and 18‐day‐old rat pups in isolation and the home cage

“…The two younger groups replicated the increases in activity seen when the drug was administered centrally and peripherally (Barr et al, in press;Jackson & Kitchen, 1989). However, 18-day-old pups were less active when drugged, did less rising and wall climbing, and were impaired on two tests of motor reflex.…”

Kappa opioid mediated locomotor activity in the preweanling rat: role of pre- and postsynaptic dopamine receptors

“…In direct contrast to the adult, kappa opioid agonists markedly enhance, rather than depress, the locomotor activity and wall climbing of preweanling rats (Jackson and Kitchen 1989;Carden et al 1991;Kehoe and Boylan 1994;Bolanos et al 1996;Duke et al 1997a). The mechanisms mediating the behavior activating effects of kappa opioid agonists are not known; however, they are sensitive to dopaminergic manipulation, since U-50,488-induced locomotor activity is attenuated by both a nonselective DA receptor antagonist (flupenthixol) and agonist (NPA) (Duke et al 1997a).…”

Indirect dopamine agonists augment the locomotor activating effects of the ?-opioid receptor agonist U-50,488 in preweanling rats

“…Dramatically different be-havioral effects are observed when preweanling and fetal rats are treated with -opioid receptor agonists. More specifically, U-50,488 and enadoline substantially increase the locomotor activity, rearing, and general motor movements of preweanling and fetal animals (Carden, Davachi, & Hofer, 1994;Jackson & Kitchen, 1989;Kehoe & Boylan, 1994;McLaughlin, Tao, & Abood, 1995;Petrov et al, 1994;Smotherman, Moody, Spear, & Robinson, 1993). It is uncertain why -opioid receptor agonists produce such pronounced ontogenetic behavioral differences, but one possibility is that the interaction between the -opioid and dopamine (DA) systems is immature during the preweanling period and the nature of this interaction changes with further development.…”