Dopamine receptor sensitivity following nigrostriatal lesion in the aged rat

This investigation sought to determine whether the ability to regulate dopamine receptor sensitivity following removal of dopaminergic innervation is altered during aging. Aged (24-26 months old) Fisher 344 rats compared with young (6 months old) rats had lower levels of dopamine and dopamine receptor binding ([3H]ADTN), but no change of dopamine-stimulated adenylate cyclase activity. Unilateral lesion of the nigrostriatal pathway produced equivalent dopaminergic denervation in rats of both age groups. The denervated striata of young rats had greatly enhanced dopaminergic sensitivity as evidenced by apomorphine induced rotational behavior and increased dopamine stimulated adenylate cyclase activity and [3H]ADTN binding. Old rats responded similarly with a very high degree of increased dopaminergic sensitivity in both the behavioral and biochemical parameters, demonstrating that the ability to regulate dopamine receptors remains basically intact. However, deficits of supersensitivity occurred in apomorphine induced rotational behavior and [3H]ADTN binding and there was a large deficit in the guanine nucleotide sensitive subcomponent of [3H]-ADTN binding. Supersensitivity of dopamine stimulated adenylate cyclase was not altered. The diminished ability to develop supersensitivity to [3H]ADTN binding could contribute to decreased [3H]ADTN binding in unlesioned rats.