Effects of route of administration on cocaine induced dopamine transporterblockade in the human brain

The route of administration influences the reinforcing effects of cocaine. Here we assessed whether there were differences in the efficacy of cocaine to block the dopamine transporters (major target for cocaine's reinforcing effects), as a function of route of administration. Positron emission tomog raphy and [C-11]cocaine, a dopamine transporter radioligand, were used to c ompare the levels of dopamine transporter blockade induced by intravenous, smoked and intranasal cocaine in 32 current cocaine abusers. In parallel, t he temporal course for the self-reports of "high" were obtained. Cocaine si gnificantly blocked dopamine transporters. The levels of blockade were comp arable across all routes of administration and a dose effect was observed f or intravenous and intranasal cocaine but not for smoked cocaine. For equiv alent levels of cocaine in plasma and DAT blockade, smoked cocaine induced significantly greater self reports of "high" than intranasal cocaine and sh owed a trend for a greater effect than intravenous cocaine. The time to rea ch peak subjective was significantly faster for smoked (1.4 +/- 0.5 min) th an for intravenous cocaine (3.1 +/- 0.9 min), which was faster than intrana sal cocaine (14.6 +/- 8 min). Differences in the reinforcing effects of coc aine as a function of the route of administration are not due to difference s in the efficacy of cocaine to block the dopamine transporters. The faster time course for the subjective effects for smoked than intravenous and for intravenous than for intranasal cocaine highlights the importance of the s peed of cocaine's delivery into the brain on its reinforcing effects. (C) 2 000 Elsevier Science Inc, All rights reserved.