An alternative explanation is that 5 HT3 antagonists affect only specific habits and that the specificity is connected with either the principle neurotransmitters and/or brain regions active in the behavior. All behaviors noted above have now been shown tO include head dopamine although the relative participation of the mesolimbic and nigrostriatal programs antigen peptide may differ. In this regard, 5 HT3 receptors have been located in the mesolimbic and nigrostriatal dopamine pathways. Sorenson et al. found that S HTj antagonists decrease dopamine firing charges both in AlO and A9. Similarly, 5 HT3 antagonists block dopamine release in both nucleus accumbens and striatum. It should be noted that under some conditions 5 HT3 antagonists seem to have postsynaptic actions. Tyers et al. Discovered that the hyperactivity typically caused by infusion of dopamine in to the nucleus accumbens is inhibited by ICS 205 930. In our study, we have a) investigated the effects of multiple 5 HT3 antagonists on cocaine induced adhd, b) investigated some alternative mechanisms of 5 HT3 fatty acid amide hydrolase inhibitors action, and c) investigated the requirement of Organism endogenous serotonin for the 5 HT3 antagonist inhibition of cocaine induced locomotion. The 5 HT3 antagonists zacopride, ICS 205 930, and MDL 72222 were used to behaviorally assess the effectiveness of structurally different compounds. ICS 205 930 and MDL 72222 are tropane types, zacopride isn’t. 2|8 Carbomethoxy 3,8 tropane, a top affinity phenyltropane cocaine analog, was used to find out if S HTj antagonists restrict cocaine receptor binding to the striatal dopamine transporter. Madras et al. Show that the precise dopamine uptake blockers inhibit striatal WIN 35,428 presenting by 90%. They have also shown that cocaine and cocaine congeners fully displaces WIN 35,428 binding. We used lH]WIN 35,428 to examine if 5 HT3 antagonists restrict cocaine caused locomotion by way of a) order Dizocilpine right blocking cocaines power to bind with the cocaine receptor and/or b) interacting with the dopamine binding websites on the transporter. Animals were pretreated with / chlorophenylalanine for 3 days to lessen 5 HT amounts to endogenous by 90% and then challenged with zacopride and crack, to determine the role of endogenous 5 HT. WIN 35,428 was received from Du Pont New England Nuclear. Zacopride was generously given by Wyeth Ayerst. ICS 205 930 and MDL 72222 were acquired from Research Biochemicals, Inc.. Drug and PCPA were obtained from Sigma Chemical Co.. Male Sprague Dawley rats weighing between 250 300 g were used. Animals were preserved on a 12 L: 12 D schedule and provided with water and food ad lib. Animals were divided in to five subgroups on the cornerstone of pretreatment with saline, zacopride, ICS 205930, or MDL 72222.