CIRCADIAN PHASE-SHIFTING INDUCED BY CLONIDINE INJECTIONS IN SYRIAN-HAMSTERS

The mammalian circadian pacemaker can be phase shifted by photic, pharmacological, and behaviorally-derived stimuli. The phase-response curves (PRCs) characterizing these diverse stimuli may comprise two distinct families; a photic PRC typified by the response to brief light pulses, and a nonphotic PRC, typified by the response to dark pulses and to behavioral activation. The present study examined the phase shifting effects of acute systemic treatment with the alpha2-adrenoceptor agonist, clonidine, in Syrian hamsters. Clonidine injections (0.25 mg/kg, ip) delivered during subjective night mimicked the phase shifting effects of light pulses in animals housed in both constant darkness (DD) and constant red light (RR), but similar effects were not seen in saline-treated controls. Both clonidine and saline injections resulted in phase advances during subjective day, but only in RR-housed animals. Clonidine-induced phase shifting was dose-dependent, but rather high doses were required to induce phase shifts. Pretreatment with the selective noradrenergic neurotoxin, DSP-4, blocked clonidine-induced phase shifting. These results suggest that clonidine acts at presynaptic alpha2-adrenergic autoreceptors to disinhibit spontaneous and/or evoked activity in the photic entrainment pathway.