Behavioural responses to the selective D1‐dopamine receptor agonist R‐SK&F 38393 and the selective D2‐agonist RU 24213 in young compared with aged rats

Abstract

In aged male Sprague-Dawley rats (22 months) with a selective loss of D2- but not of D1-dopamine receptors, stereotyped behaviour induced by 0.5 mg kg-1 apomorphine was increased and prolonged in comparison with young (4 month) counterparts. This suggested a pharmacokinetic effect rather than a pharmacodynamic change. The syndrome of non-stereotyped behavioural responses to the selective D1-agonist R-SK&F 38393, 1.25-20.0 mg kg-1, was unchanged in aged vs young animals, but the topography of individual behaviours constituting this overall syndrome was altered with aging. Neither the overall syndrome of low intensity stereotyped behaviour nor the topography of individual behaviours induced by the selective D2-agonist RU 24213, 1.25-20.0 mg kg-1, were altered in aged vs young animals. Loss of D2- but not D1-receptors with aging was therefore found to be associated with no change in responsivitiy to a D2-receptor agonist. The decreased intense grooming and increased vacuous chewing responses to the D1-agonist with aging parallel the previously demonstrated effects of selective D2-antagonists on these D1-stimulated behaviours. It is suggested that age-related decline in D2-receptor activity may have greater functional consequences in relation to D1-:D2-interactions than in simply influencing responsivity to a D2-agonist. Such interactive effects should be taken into account when considering the pathophysiology and treatment of age-related extrapyramidal movement disorders.