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KD Parfitt, A Gratton and PC Bickford-Wimer
Veterans Administration Medical Center, Denver, Colorado.
The effects of the selective dopamine D1 and D2 receptor agonists, SKF 38393 and N-0437, respectively, on the firing rate of medial prefrontal cortex (PFC) neurons were studied in young (3-5 months old), and aged (18 and 26 months old) Fischer 344 rats. Multibarrel glass micropipettes, filled with 1 mM SKF 38393 and N-0437, were lowered into the anteromedial cortical target area (PFC) of the mesocortical dopamine system in urethane-anesthetized animals. The drug solutions were locally applied by pressure ejection. In young rats, both agonists produced dose-dependent and reversible reductions in firing rates. However, the D2 agonist was approximately 10 times more potent than the D1 agonist in suppressing firing rate. Even at the highest doses, SKF 38393 rarely produced complete cessation of firing in PFC cells. Moreover, no evidence of synergism was observed when the two drugs were simultaneously applied. PFC neurons in aged rats were significantly subsensitive to locally applied SKF 38393, whereas no change in sensitivity to N-0437 was observed. These results suggest that both D1 and D2 receptors are present in the PFC and that agonist occupancy of each of these receptors elicits an inhibition of PFC neuron discharge; furthermore, these data suggest an age-related change in D1 dopamine receptor-mediated processes with no concomitant change in processes linked to the activation of D2 dopamine processes.
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