Behavior and binding: correlations between alpha 1-adrenergic stimulation of acoustic startle and alpha 1-adrenoceptor occupancy and number in rat lumbar spinal cord.
The relationship between alterations in alpha 1-adrenoceptors and behavioral effects of alpha 1-adrenergic agonists were investigated in a localized region of the rat central nervous system. Direct infusion of the alpha 1-adrenergic agonists, D-amphetamine or phenylephrine. into the subarachnoid space of the lumbar cord (intrathecal administration) increased the amplitude of the acoustic startle reflex, The magnitude of this behavioral facilitation correlated highly with the degree of alpha 1-adrenoceptor occupation measured by [3H]prazosin binding in lumbar spinal tissue. Using an in vitro estimate of receptor occupation, maximal potentiation of startle occurred following approximately 30% occupation of the receptors, using either D-amphetamine or phenylephrine. Intrathecal administration of 6-OHDA produced a 95% decrease in spinal norepinephrine and markedly enhanced the behavioral response to intrathecal phenylephrine as well as the number of alpha 1-adrenoceptors. The correlation between the time course of the behavioral and binding changes was 0.99. No change in receptor affinity (KD) or receptor occupation by phenylephrine was found after 6-OHDA. The data indicate that receptor binding parameters do have predictive value for behavior, especially if localized regions of the nervous system, critical to the behavior, are analyzed.
D000161:Acoustic Stimulation; D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D003913:Dextroamphetamine / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology; D016627:Oxidopamine; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D010656:Phenylephrine; D016627:Oxidopamine; D003913:Dextroamphetamine; D009638:Norepinephrine; D011224:Prazosin