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Title: Interactions between dopamine and glutamate receptors and their roles in motoric and rewarded behaviours
Author: Newton, J. M.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 1999
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The effects of a novel AMPA antagonist, LY293558, on reward and motor performance in rats, were compared with compounds known to be active in the mesolimbic dopamine reward system. Drugs were given systematically or directly into the core of the nucleus accumbens and reinforcing properties were assessed by two reward paradigms (brain stimulation and consumption of sucrose solutions). LY293558, administered by either route, significantly suppressed spontaneous locomotor activity in naive rats. Direct (but not systemic) antagonist injection significantly stimulated locomotion in habituated rats. As expected, when administered by either route, haloperidol blocked whereas MK-801 and amphetamine, stimulated locomotor activity. LY293558 had no significant effect on the rewarding properties of brain stimulation when injected by either route but produced a significant motor impairment. Systematic administrations of MK-801 and amphetamine facilitated whereas haloperidol inhibited reinforcement behaviour as measured by brain stimulation. Direct injections of these compounds into the core of the nucleus accumbens, had no significant effect on reward function, although haloperidol depressed rates of responding, an effect due to motor impairment. When given by either route, LY293558, MK-801 and haloperidol all suppressed consumption of sucrose solution in a two-bottle preference test. These decreases in consumption corresponded to doses that impaired motor function. In conclusion, LY293558 has effects on locomotor activity that depend on dose and route as well as previous experiences of the apparatus and the drug. Its effects on brain stimulation and consumption of sucrose solution are primarily mediated by motor effects, supporting the claimed link between the nucleus accumbens core and motor function.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available