In the present study we investigated the in vivo pharmacological profile of the benz[e]
indole cis-8-hydroxy-3-(n-propyl)],2,3a,4,5,9b-hexahydro-1H-benz[e]
indole (cis-8-OH-PBZI), which has been described as a preferential
dopamine D3 receptor agonist in vitro. The compound inhibited spontaneous locomotor activity in mice, an effect which was antagonized by the
dopamine D3 receptor antagonist 5,6-dimethoxy-2-(di-u-propylamino)
indan (U99194A). Moreover,
cis-8-OH-PBZI inhibited conditioned avoidance responding in rats, a preclinical test indicative of
antipsychotic efficacy, at doses which did not induce
catalepsy. Doses of
cis-8-OH-PBZI (6 and 12 mg/kg) that inhibited spontaneous locomotor activity in rats did not affect interstitial levels of
dopamine and dihydroxyphenylacetic
acid (
DOPAC) in the nucleus accumbens or dorsolateral striatum. In contrast to the effect of the
dopamine receptor agonist (+/-)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphythalene (7-OH-DPAT),
cis-8-OH-PBZI did not induce locomotor activity in reserpinized mice. In conclusion,
cis-8-OH-PBZI exhibits a pharmacological profile that suggests it has
antipsychotic activity but lacks the motoric side effects often associated with
antipsychotic medication. The data suggest a mechanism requiring the activation of postsynaptic
dopamine D3 receptors and support the hypothesis that these receptors mediate inhibitory behavioral effects.