Behavioural microanalysis of dopamine autoreceptor function

Muscat, Richard (1987) Behavioural microanalysis of dopamine autoreceptor function. Doctoral thesis, City of London Polytechnic.


Low doses of dopamine autoreceptor (DA) agonists are presumed to act by stimulating DA autoreceptors on the sona/dendrites and axon terminals of DA neurons. Low doses of apomorphine reduced food Intake, in a microstructural analysis paradigm, by reducing both the time spent feeding and the rate of food ingestion. The reduction of eating time was shown to result from the stimulation of DA autoreceptors located on the cell bodies and dendrites of the mesolimbic DA system. The reduction of eating rate however, appeared to result from the activation of axon terminal DA autoreceptors. The significance of this dissociation is discussed in relation to the mechanisms through which presynaptic DA receptors on the same neuron may subserve different behavioural functions.

The observation that apomorphine administration resulted in a selective manipulation of the microstructural parameters of feeding, was then used to assess the action of antidepressant drugs on DA autoreceptor function. In both normal and chronically stressed rats, chronic antidepressant treatment failed to alter the sensitivity of DA autoreceptors. However, on withdrawal, the sensitivity of cell body DA autoreceptors appeared reduced, as apomorphine no longer in any way influenced the time spent feeding in the microstructural paradigm. The Implications of these findings are discussed in relation to the hypothesis that antidepressant drugs increase DA function by reducing the sensitivity of presynaptic DA receptors.

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