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|Title:||Functional Consequences and Mechanism of Lsd Action in the Lateral Eye of Limulus|
|Author(s):||Kass, Leonard James|
|Department / Program:||Physiology and Biophysics|
|Degree Granting Institution:||University of Illinois at Urbana-Champaign|
|Subject(s):||Biology, Animal Physiology|
|Abstract:||I have used an electrophysiological approach to explore the effects of LSD action on lateral inhibition in the lateral eye of Limulus. I recorded extracellular and intracellular responses from eccentric cells while producing inhibition via light and antidromic stimulation in the presence of 5-HT, LSD, chlorimipramine, and a bathing medium high in Mg('++) and low in Ca('++) which partially or completely blocks synaptic transmission.
On the basis of experimental evidence presented in Section I, I propose the following hypothesis for LSD action at the lateral inhibitory synapse: In 1-5 (mu)M LSD, partial blockade of presynaptic sites for reuptake prolongs inhibitory transmitter lifetime in the synaptic cleft and thereby enhances inhibition; in 5-20 (mu)M LSD, more sites are blocked leading to accumulation of synaptic transmitter and consequently to postsynaptic desensitization.
In Section II, I use linear systems analysis to quantify the pharmacological effects of LSD on the dynamics of lateral inhibition. Light-to-spike transfer functions of singly illuminated eccentric cells reveal the drug's effect on the light-transducing or spike-encoding mechanisms. Transfer functions of light-evoked lateral inhibition or antidromically stimulated inhibition reveal time and frequency-dependent changes that occur as a result of LSD's action at the inhibitory synapse. The changes observed in these transfer functions are the following: (1)the dynamics of lateral inhibition at both low and high concentrations of LSD is slowed, as indicated by the increased phase lag in lateral inhibitory transfer functions; (2)the magnitude of lateral inhibition decays, perhaps desensitizes, more rapidly in the presence of LSD than in the normal eye. These changes in the dynamics or time course of lateral inhibition in the presence of LSD are shown to be compatible with the presynaptic uptake blockade hypothesis for LSD action described in Section I.
In Section III, I account for the experimental evidence obtained by other investigators of LSD's action in the mammalian brain in terms of the presynaptic uptake blockade hypothesis. The major findings on LSD's actions in the mammalian brain are the following: (a)LSD can antagonize the inhibitory effects of iontophoresed or synaptically released 5-HT; (b)LSD competes with 5-HT for high affinity binding sites in synaptosomal membrane fractions; (c)LSD can "mimic" the inhibitory effects of 5-HT; (d)LSD can "facilitate" or enhance 5-HT inhibition; (e)the actions of LSD appear to be concentration dependent; (f) systemically administered LSD raises the concentration of 5-IAA, the metabolite from 5-HT breakdown. All of these findings are shown to be consistent with the presynaptic uptake blockade hypothesis, a hypothesis invented to account for the diverse actions of LSD (Sections I and II) found in Limulus lateral eye.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1981.
|Date Available in IDEALS:||2014-12-14|
This item appears in the following Collection(s)
Dissertations and Theses - Molecular and Integrative Physiology
Graduate Dissertations and Theses at Illinois
Graduate Theses and Dissertations at Illinois