It has been suggested that activation of dopamine D1-like and D2-like receptors contribute equally to the maintenance of drug self-administration. This study compared the contribution of these receptor subtypes to 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MA) self-administration. Effects of pretreatment with the D2-like receptor antagonist, eticlopride (0.0, 0.0125, 0.025 or 0.05 mg/kg, intraperitoneal), on responding maintained by several doses of MDMA (0.5, 1.0 and 2.0 mg/kg/infusion) and MA (0.05, 0.1 and 0.2 mg/kg/infusion) were determined. As we have published data showing the effects of the D1-like receptor antagonist, SCH23390 (0.0, 0.01 or 0.02 mg/kg, subcutaneous), on MDMA self-administration, effects of this dose range on the MA dose-response curve were determined. In our previous study, 0.02 mg/kg SCH23390 produced a rightward shift in the MDMA dose response curve, whereas in the present results, this dose decreased responding maintained by most doses of MA. Eticlopride increased the responding maintained by most doses of MDMA but failed to alter MA self-administration. The present results suggest that both D1-like and D2-like receptors contribute to the maintenance of MDMA self-administration, whereas MA self-administration was more sensitive to D1-like receptor blockade.

Nicotine self-administration in rats is the most widely used animal model of tobacco dependence. There is increasing evidence, however, that non-nicotinic constituents in smoke contribute to addiction and that different tobacco products contain varying levels of these constituents. The present study firstly sought to compare self-administration of pure nicotine to tobacco particulate matter (TPM) to determine if there were differences in reward-efficacy attributable to the non-nicotine constituents. Secondly, cigarette and roll-your-own (RYO) TPM groups were included and compared to determine whether different formulations of non-nicotinic constituents could impact reward. Briefly, male Sprague Dawley rats were implanted with indwelling jugular catheters for self-administration (n = 76). The reinforcing efficacy of infusions of nicotine (0.0 or 30.0 μg/kg/infusion) versus cigarette/RYO TPM (with matched nicotine content) was determined using spontaneous acquisition of self-administration on a fixed ratio schedule. The progressive ratio schedule was then employed to determine the motivation to receive each drug and within-subject dose-response curves were also produced (7.5, 15.0, 30.0 and 60.0 μg/kg/infusion nicotine). The main finding was that the RYO TPM was more reinforcing and produced a different profile of reward-related behaviour compared with both the nicotine and the cigarette TPM groups. The conclusions were that non-nicotinic components have a role in tobacco dependence and that some tobacco products could have higher abuse liability, irrespective of nicotine levels.

These data are consistent with the idea that high dose MDMA exposure produces neuroadaptations that exhibit recovery with extended abstinence from the drug.

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