Age-related changes of dopamine sensitive cyclic AMP generation in the rat frontal cortex

The dopamine (DA) D-1 and D-2 receptors coupled to 3',5'-cyclic adenosine monophosphate (cAMP) generation were studied in membrane particles of the frontal cortex in young (3-month-old), adult (12-month-old) and aged (24-month-old) male Sprague-Dawley rats. Activation of D-1 receptors with DA, apomorphine or fenoldopam enhanced accumulation of cAMP in the frontal cortex of young rats. The stimulatory effect elicited by DA on cAMP generation declined by about 20% in adult rats. No further decline in cAMP accumulation was noticeable in aged animals. The response to dopaminergic agonists was blocked by the D-1 receptor antagonist SCH 29390 in the three age groups examined. The presence of D-2 receptors, negatively coupled to cAMP generation, was demonstrated by incubating frontal cortex membrane particles with SCH 23390 and then with DA. This inhibitory response, was also elicited with D-2 receptor agonists quinpirole or bromocriptine in the absence of SCH 23390 in which these compounds produced a decrease in cAMP. The decrease in cAMP caused following D-2 receptor stimulation was shown to be enhanced with age. No difference was observed between the three age groups of animals in the activation of cAMP production by forskolin. The present data suggest a selective decrease in the coupling between the D-1 receptor and cAMP generation in the frontal cortex of adult and aged rats and of an age-dependent increase in the coupling between the D-2 receptor and cAMP inhibition. The functional consequences of these biochemical changes may have important implications in the aging of the rat frontal cortex.