Development of Biphasic Dose-respose to Clonidine, Alpha-Adrenergic Agonist in CNS.
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Clonidine, alpha-adrenergic agonist in the central nervous system, was injected into Sprague-Dawley rats in order to attain a quantitative dose-dependent resp,onse as reflected by changes in activity. Injections were administered intra-peritoneally, doses ranging from 0.05 mg/kg to 5.0 mg/kg. Resulting activity was then mechanically m6nitored in electronic motility meters for a period of one hour. It was found that doses less than 0.25 mg/kg produced an inhibitory effect upon activity counts, while doses higher were progressively stimulatory in a clear-cut biphasic dose response. Other peripheral effects of alpha-adrenergic arousal followed the S8_me pattern of response. This evidence provides not only insight into the specific mechanism of clonidine, but provides support for the presently developing theory of neurotransmission involving the interaction of pre- and post-synaptic receptors. It is theorized that at low doses the agonist stimulates presynaptic autoreceptors and their resulting impulse inhibition, while at higher doses the drug proves to be stimulatory. Evidence such as this will be useful in future treatment and understanding of behavioral disorders such as manic-depression and schizophrenia.