Dopamine receptor subtypes and ingestive behaviour

Abstract

Both centrally and systemically administered dopamine agonists and antagonists decrease ingestive behaviour. The aim of this thesis was to examine whether drugs acting at different receptor subtypes decreased intake in different ways. A microstructural analysis was used to examine dopaminergic drug effects on licking behaviour. A dopamine D3 receptor agonist, 7-OH-DPAT, a dopamine D2 receptor antagonist raclopride and a mixed dopamine D2/D3 agonist quinpirole were compared in this paradigm. These drugs reduced the number of licks by differentially decreasing parameters which are thought to reflect the palatability of the stimulus such as mean bout duration of licking and the initial rate of licking. Follow-up experiments were conducted to further examine the possibility that motor deficits were underlying decreases in licking parameters. The effects of raclopride and 7-OH-DPAT were compared to the effects of a dopamine Dl antagonist SCH- 23390 and were analysed using a brief contact licking test. Again, the behavioural expression of anorexia induced by these drugs seemed to rely on a differential decrease in mean bout duration. Results also revealed that the three drugs used differed in the extent to which they produced a motoric deficit Attempts to block the effects of 7-OH-DPAT on licking (wameters were made by using the putative D3 receptor antagonists PNU-99194A and amisulpride. In addition, the effects of these drugs alone on licking behaviour were examined PNU-99194A failed to block the effects of 7-OH-DPAT and was relatively ineffective in producing changes in licking behaviour when administered alone. Amisulpride blocked the effects of 7-OH-DPAT only at high doses and when injected alone produced an increase in intake through an increase in mean bout duration of licking. Results from Chapters 4,5 and 6 suggested that 7-OH-DPAT was having an effect on palatability. Therefore, Chapter 7 presents an experiment which examines the effect of 7-OH-DPAT on the licking behaviour of rats which encounter a devaluation of reward (successive negative contrast). 7-OH-DPAT reduced successive negative contrast leading to the proposal that D3 receptors may mediate relative as well as absolute reinforcer value. These results bear important implications for understanding the role of dopamine receptor subtypes in components of food reward and appetitive behaviour in general and may well have implications for the treatment of eating disorders.