Upregulation of (+)-7-hydroxy-N,N-di-n-[3H]propyl-2-aminotetralin binding following intracerebroventricular administration of a nitric oxide generator.

Abstract

Nitric oxide modulation of dopamine D2 and D3 receptor binding was examined using [125I]epidepride (D2) and (+)7-hydroxy-N,N-di-n-[3H]propyl-2-aminotetralin ([3H](+)-7-OH-DPAT, D3). Nitric oxide, generated by i.c.v. injection of S-nitroso-N-acetyl-penicillamine (SNAP; 5 microg or 10 microg), significantly increased the density of [3H](+)-7-OH-DPAT binding sites (39% and 134%, respectively) in the striatum 24 hours post-injection in the absence of Gpp(NH)p, representing an upregulation of either D3 receptors or high affinity D2 receptors. In the presence of 10 microM Gpp(NH)p, D3 receptor upregulation was maintained in both the 5 microg (increased 35%) and 10 microg SNAP (increased 44%) groups. [3H](+)-7-OH-DPAT binding was reduced in both striatum and nucleus accumbens in the presence of 10 microM Gpp(NH)p compared to binding in the absence of Gpp(NH)p, suggesting an upregulation of D3 receptors. Administration of SNAP did not alter total specific [125I]epidepride binding in either brain region. These data suggest that; 1) D3 receptor density is modified following nitric oxide generation, and 2) the density of high affinity D2 receptors identified by [3H](+)-7-OH-DPAT increases in the striatum, but decreases in the nucleus accumbens.