Absent Skin Conductance Response (SCR) in pathological gambling (PG) may relate to dopaminergic mechanisms. We recruited equal numbers of PG subjects and healthy control (HC) subjects, and then tested the claim that SCR is less conditioned by dopaminergic activity in PG subjects. During active gambling, SCR differed in PG and HC subjects (P < 0.05), but positron emission tomography revealed the same dopamine receptor availability. However, highly sensation-seeking (HS) PG subjects had lower dopamine receptor availability (P < 0.0001) in the baseline, compared to normal sensation-seeking (NS) PG subjects. We find that HS versus NS controls had the same observation of significant increase of binding potential (BP(ND)) in high compared to normal sensation seekers. In both groups, PG and HC, highly sensation-seeking subjects had significant increase of receptor availability in striatum, compared to normally sensation-seeking subjects, separately (P < 0.05 and P = 0.02, respectively) and together (P < 0.0005). We conclude that SCR is less conditioned by dopaminergic activity in highly sensation-seeking subjects, regardless of PG status