Monoamine depletion attenuates the REM sleep deprivation-induced increase in clonidine response in the forced swimming test.
Effect of monoamine depletion on the REM sleep (REMs) deprivation-induced increase in clonidine response in the forced swimming test was investigated. Mice were deprived of REMs by the small pedestal method. Clonidine HCl (10-1000 micrograms/kg, IP), an alpha 2-adrenoceptor agonist, dose dependently increased swimming activities in group-housed and socially isolated mice used as the control groups. The dose-response relationship shifted to the left following REMs deprivation (ED50 values in the group-housed, isolated, and REMs-deprived mice were 250, 200, and 27 micrograms/kg, respectively). Monoamine depletion, induced by reserpine (5 mg/kg, IP) plus alpha-methyl-p-tyrosine (250 mg/kg, IP), did not produce any changes in the effects of clonidine in the control groups. However, in REMs-deprived mice, monoamine depletion significantly decreased the effect of 100 micrograms/kg clonidine, but not that of 300 micrograms/kg clonidine on swimming activity. These results indicate that clonidine-induced increase in swimming activity in the forced swimming test is mainly mediated by postsynaptic alpha 2-adrenoceptor, and that endogenous noradrenaline in the brain plays an important role in the increase of clonidine response following REMs deprivation treatment. The neuronal mechanism of the increase in clonidine response is discussed.
Asakura
W
W
Division of Pharmacology, Toyama Medical and Pharmaceutical University, Japan.
Matsumoto
K
K
Ohta
H
H
Watanabe
H
H
D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D003863:Depression / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D012892:Sleep Deprivation / Q000502:physiology*; D012895:Sleep, REM / Q000502:physiology*; D012934:Social Isolation; D013550:Swimming; D019805:alpha-Methyltyrosine
D058669:Adrenergic alpha-2 Receptor Antagonists; D015306:Biogenic Monoamines; D008781:Methyltyrosines; D018341:Receptors, Adrenergic, alpha-2; D019805:alpha-Methyltyrosine; D012110:Reserpine; D003000:Clonidine