European journal of pharmacology
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Prior studies indicate long-term reductions of striatal dopaminergic markers after sustained, high dose methamphetamine exposures in vivo, suggesting a neurotoxic effect. We have reported lack of regulation of vesicular monoamine transporter type-2 expression, as opposed to other markers of striatal dopaminergic terminals, under conditions that alter dopaminergic transmission without synaptic terminal losses. In the present study, we evaluated the vesicular monoamine transporter and the neuronal membrane dopamine transporter in rat striata after in vivo exposure to neurotoxic or to intermittent, low dose (behaviorally-sensitizing, non-neurotoxic) methamphetamine administrations. ⋯ Neurotoxic methamphetamine treatment reduced both striatal vesicular monoamine transporter (-26%) and dopamine transporter (-39%) bindings. There were no changes after the non-neurotoxic treatment regimen. The vesicular monoamine transporter may thus be a valuable marker in the further clinical study of psychostimulant drug neurotoxicity.
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Intraplantar co-administration of sub-anesthetic doses of bupivacaine (2.5 microg) or lidocaine (7.5 microg) increased the dose- and time-dependent analgesic effects of the 5-HT3 receptor antagonist, 3-a-tropanyl-1-H-indole-3-carboxylic ester (ICS-205 930) (1-100 microg; 50 microl) against inflammatory pain induced by hindpaw inoculation with complete Freund's adjuvant. The effects of bupivacaine were greater than lidocaine at all doses of ICS-205 930 tested. These findings may reflect facilitation of ICS-205 930 effects through negative allosteric modulation by bupivacaine and lidocaine of peripheral 5-HT3 receptors involved in nociceptive processing.