Norepinephrine elicits both excitatory and inhibitory responses from Purkinje cells in the in vitro rat cerebellar slice.
Superfusion of Purkinje neurons in the in vitro rat cerebellar slice with norepinephrine caused increases and decreases of spontaneous Purkinje cell firing. Excitations were evoked by low concentrations of norepinephrine (0.5-10 microM) and by the beta receptor agonist isoproterenol (0.1-5 microM). These excitations were reduced by timolol (1-2 microM), a beta receptor antagonist. Perfusion with higher concentrations of norepinephrine (greater than 16 microM), caused a depression of Purkinje neuron spontaneous activity. This inhibitory response was blocked by the alpha receptor antagonist phentolamine. The alpha 1 selective agonist phenylephrine had no effect on spontaneous activity at concentrations up to 100 microM, but the alpha 2 selective agonist clonidine (1-50 microM) elicited decreases in firing rate. These responses appeared to be due to a direct action on Purkinje cells, because neither the excitation nor the depression of Purkinje neuron activity elicited by norepinephrine was substantially altered when tested in a medium which substantially blocked synaptic transmission within the slice. Under these in vitro conditions, norepinephrine appears to increase the firing rate of Purkinje neurons via an interaction with beta adrenergic receptors, while norepinephrine induced depressions may be linked to alpha adrenergic receptor interactions; both receptors appear to be located directly on the Purkinje neurons.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002531:Cerebellum / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D010656:Phenylephrine; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine