Dissociation of locomotor impairment from mydriasis evoked by clonidine injected into cat's rostral hypothalamus.

The anterior hypothalamic preoptic area (AH/POA) was examined as a possible site of action of clonidine and other alpha noradrenergic receptor agonists which evoke motor and autonomic changes. Chronically indwelling guide cannulae were implanted stereotaxically in the diencephalon of the cat. Following post-operative recovery, a micro-injection into AH/POA was made in a volume of 1.0 microliter of one of the following compounds: 5.0-50.0 micrograms clonidine, 5.0-50.0 micrograms norepinephrine, 5.0-50.0 micrograms phenylephrine and 5.0-50.0 micrograms methoxamine. The smallest dose of 5.0 micrograms clonidine produced a brief period of restlessness, licking, retching and emesis but a much longer-lasting mydriasis. When the dose of clonidine was raised to 20 micrograms, the cat became behaviorally sedated, after a latency of about 15 min, for a period of up to 1.0-2.0 hr. This was accompanied by a prolonged period of mydriasis and preceded by a short interval of restlessness, licking, retching and emesis. After the highest dose of 50.0 micrograms clonidine was micro-injected in AH/POA, a profound impairment of motor activity, adynomia and restlessness developed within 15-20 min, persisted for 30 to 60 min and was accompanied also by mydriasis with maximal pupillary dilation lasting for up to six hr. When 5.0-50.0 micrograms phenylephrine or 5.0-50.0 micrograms norepinephrine were micro-injected at clonidine-reactive sites in AH/POA, only rarely were brief instances of restlessness, licking, retching and emesis observed; however, methoxamine at all doses tested failed to produce any visible signs of autonomic or motor disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)