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Title: Use of genetic strains to explore the influence of stress responsivity on the effects of psychostimulant drugs
Author: Rado, T. A.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 1999
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In the present thesis, the Lewis strain, known to show a reduced corticosterone response to stressors relative to outbred Sprague-Dawleys, were more sensitive to the locomotor activating and stereotypy-inducing effects of d-amphetamine (0.75 - 3.0 mg/kg) than the Fischer strain, known to show an enhanced corticosterone response to stressors relative to outbred Sprague-Dawleys. The strains did not differ in their response to the acute locomotor activating effects of cocaine (10.0 - 40.0 mg/kg). Only Lewis rats showed place conditioning to d-amphetamine (0.25 - 1.0 mg/kg). In an initial drug sensitization (context-dependent) study, Lewis rats were more susceptible than Fischer rats to the sensitizing effects of cocaine. However, additional cocaine sensitization studies revealed a more complex array of findings. The appearance of cocaine-induced sensitization in either strain was found to be dependent upon a number of factors, including inter-injection interval (1 or 4 days), the environment where drug treatments were experienced, and drug dose. Importantly, both strains could display sensitization to cocaine. Fischer rats were more sensitive than Lewis rats to the acute locomotor activating and sensitizing effects of the D2/D3 agonist quinpirole, but, once again, the appearance of sensitization was dependent upon a number of factors (as described above for cocaine). The findings emphasise the complex behavioural effects of drugs acting on dopaminergic systems in the Fischer and Lewis strains of rat. They do not support the current, but contradictory, hypotheses that: a) the highly stress-responsive strain (Fischer) are consistently more susceptible to the behavioural activating (and reinforcing effects) of psychostimulants, and b) the so-called "addiction prone" strain (Lewis rats) are consistently more susceptible to the same effects.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available