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

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 μg or 10 μg), 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 μM Gpp(NH)p, D₃ receptor upregulation was maintained in both the 5 μg (increased 35%) and 10 μg SNAP (increased 44%) groups. [³H](+)-7-OH-DPAT binding was reduced in both striatum and nucleus accumbens in the presence of 10 μM 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.