The effects of GABA and benzodiazepines on neurones in the suprachiasmatic nucleus (SCN) of Syrian hamsters.
Administration of benzodiazepines at appropriate times in the circadian cycle induce phase-shifts in circadian locomotor activity. The possibility that benzodiazepine-induced shifts are mediated at the level of the suprachiasmatic nuclei (SCN), identified as the circadian pacemaker in mammals, was examined electrophysiologically. Extracellular recordings were made from Syrian hamster (Mesocricetus auratus) hypothalamic SCN neurones in vitro to assess (1) the effects of gamma-aminobutyric acid (GABA) on SCN neuronal activity and (2) the effects of benzodiazepines (chlordiazepoxide and flurazepam) on GABA-evoked responses. Of 93 SCN cells tested, 86 were suppressed by iontophoresed GABA (20 mM) in a current(dose)-dependent manner, while 6 were unaffected; suppression was found during both the projected light and dark phases of the circadian cycle. Application of bicuculline methiodide alone elevated mean discharge activity, while GABA-evoked suppressions were blocked by bicuculline (n = 9/11 cells). Iontophoresis of chlordiazepoxide or flurazepam (20 mM; 1-10 nA) alone produced a current(dose)-dependent prolonged suppression of cell firing which was antagonised by bicuculline. These results indicate that benzodiazepine/GABA-evoked responses are at least partially mediated by GABAA receptors within the SCN and suggest that SCN may be a possible locus for the action of benzodiazepines in their induction of phase-shifts in circadian function.
Mason
R
R
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Biello
S M
SM
Harrington
M E
ME
D000818:Animals; D002707:Chlordiazepoxide / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects; D006224:Cricetinae; D005071:Evoked Potentials / Q000187:drug effects; D005479:Flurazepam / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D005680:gamma-Aminobutyric Acid; D002707:Chlordiazepoxide; D005479:Flurazepam