ALTERATIONS IN BEHAVIOR AND OPIOID GENE-EXPRESSION INDUCED BY THE NOVEL TROPANE ANALOG WF-31

The effects of the acute administration of the serotonin-selective tro pane analog, [2 beta-propanoyl-3 beta-(4-isopropylphenyl)-tropane, WF- 31, on spontaneous locomotor activity were measured and compared to th ose of the highly selective serotonin uptake inhibitor, fluoxetine and cocaine, a non-selective re-uptake inhibitor of dopamine and serotoni n. WF-31 (1, 10 and 30 mg/kg)-elicited increases in locomotor behavior s when compared to vehicle-treated rats. This increased activity was b locked by pre-treatment with the dopaminergic antagonist, flupenthixol , suggesting that these effects may be mediated by dopaminergic mechan isms. Cocaine, but not fluoxetine, also elicited increases in behavior s. In addition, the effects of these three compounds on opioid peptide gene expression were also assessed using in situ hybridization histoc hemistry in the same animals. The acute administration of both WF-31 a nd cocaine increased the expression of preprodynorphin mRNA in the dor sal striatum whereas fluoxetine had no effect. Expression of striatal preproenkephalin mRNA was augmented by all three compounds. Within the nucleus accumbens, PPD mRNA levels were affected only by treatment wi th WF-31, an effect that was blocked by pre-treatment with flupenthixo l. In contrast, the acute administration of both WF-31 and fluoxetine, but not cocaine, increased the expression of preproenkephalin mRNA. T hese increases, however, were not reversed by pre-treatment with flupe nthixol. Despite its profile in vitro as a relatively selective seroto nin re-uptake inhibitor, some of the in vivo actions of WF-31 appear t o be mediated by dopaminergic mechanisms. These data further suggest t hat the mechanisms underlying expression of the opioid peptides in the nucleus accumbens may vary from those in the dorsal striatum. (C) 199 7 Elsevier Science B.V.