The abuse of psychomotor stimulants such as cocaine and methamphetamine is a continuing and very serious problem worldwide for which there is no accepted medication. Numerous lines of investigation indicate that elevation of dopamine (DA) in the nucleus accumbens (NAC) is largely responsible for the reinforcing (rewarding) effects of many classes of drugs including cocaine and methamphetamine. Although the precise mechanism of DA elevation in the NAC differs among drug classes, medications that suppress or deplete such elevation of DA may thus be useful in the treatment and prevention of diverse, destructive self-administration behaviors including excessive eating. We have pursued the chemical synthesis and identification of biogenic amine agonists and their antagonists as research tools and potential medications. In one example, we developed a practical nonchromatographic chemical synthesis of the 5-HT2A receptor antagonist MDL100,907 that is enabling numerous studies requiring this critical research tool. We have also studied the discriminative stimulus effects of MDL100,907 and several other drugs in order to gain further insight into their 5-HT receptor subtype(s) selectivity and the possible receptor role in certain neuropsychiatric disorders. We also studied MDPV to assess whether it produced thermoregulatory changes in rats as similar drugs induce such changes. We also examined whether MDPV produced taste aversion conditioning in addition to thermoregulatory changes in adolescent and adult rats. Both age groups acquired taste aversions, We found that taste aversions were developed more slowly and were weaker in the younger group and that this group increased and adults decreased body temperature following MDPV administration. There was no correlation observed in the temperature changes in either group with aversions. These results suggest that adolescents may be at higher risk for MDPV abuse than adults because of the relative insensitivity of the former group to the acquisition of aversion.
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