Noradrenergic and serotonergic mediation of the locomotor and antinociceptive effects of clonidine in infant and adult rats.

This experiment examined the necessity for intact noradrenergic and serotonergic function for the locomotor and nociceptive effects of clonidine in 10- and 100-day-old rats. Newborn rats were administered systemically 6-hydroxydopamine (100 micrograms/g; 12 and 24 hours after birth) to deplete norepinephrine (NE), and at 10 or 100 days they were injected with para-chlorophenylalanine (300 mg/kg PCPA; 5 and 24 hours before testing) to deplete serotonin (5-HT). They were then tested for the locomotor and analgesic effects of one of various clonidine doses (0, 10, 100 or 1000 micrograms/kg). Clonidine enhanced locomotion at 10 days. This effect was potentiated by NE depletion and reduced by 5-HT depletion. Clonidine reduced locomotion at 100 days, and again this was augmented by NE depletion but reduced by 5-HT depletion. NE depletion did not have an enduring effect on clonidine antinociception whereas 5-HT depletion reduced it at both ages. It is concluded that the locomotor effects of clonidine in both infant and adult rats, despite reversing with maturation, reflect its agonist action at postsynaptic alpha2 adrenoceptors. The results also add to the accumulating evidence for an early maturing and behaviorally relevant serotonergic system(s).