RESUMO
In this study, we evaluated the goldfish model of hemilabyrinthectomy for investigating potential recovery-promoting drugs. In this lesion model, the unilateral removal of the labyrinth induces a postural imbalance in response to light (Dorsal Light Reflex), from which the animals can recover over time. The behavioral effects of two neuropeptides were tested--namely, of substance P and ACTH4-10, both of which are known to promote functional recovery in several other lesion models. Furthermore, the effect of MK-801, an antagonist of the glutamatergic NMDA-receptor subtype, was tested because this substance has also been shown to exert a neuroprotective effect. After lesion of the right labyrinth, the animals (n = 12) were treated intraperitoneally daily either with vehicle (n = 12), substance P (n = 11), ACTH4-10 (n = 12), or MK-801 (n = 12). Another group (n = 11), which served as a non-lesion control, did not receive hemilabyrinthectomy or systemic injections. The lesion group, treated post-operatively with vehicle, did not recover from the postural deviation over the 24-d testing period. In contrast, all three test substances accelerated the functional recovery after unilateral labyrinthectomy. The decrease of the dorsal light reflex persisted even after cessation of drug treatment after 20 d. The results indicate that using the dorsal light reflex in the model of hemilabyrinthectomy in goldfish provides a useful approach to studying the ability of potential new neurotrophic or neuroprotective drugs to promote functional recovery.
Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Maleato de Dizocilpina/farmacologia , Orelha Interna/fisiologia , Fragmentos de Peptídeos/farmacologia , Reflexo/fisiologia , Substância P/farmacologia , Análise de Variância , Animais , Lateralidade Funcional , Carpa Dourada , Luz , Modelos Animais , Membrana dos Otólitos/fisiologia , Postura , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Reflexo/efeitos dos fármacosRESUMO
The aim of this study was to investigate whether the histamine H1-receptor blocker, chlorpheniramine (CPA), has a reinforcing effect in goldfish. We used a place-preference procedure in an aquarium with two chambers colored black and white. On day 1, the animals were placed in the test chamber for 10 min for habituation. On day 2, they were placed in the start compartment for 30 s, the sliding doors were opened, and the time spent in each compartment was recorded over the 10 min to determine the natural compartment preference for each animal. On day 3, they were injected either with 0.1, 0.4, 1.0, or 4.0 mg/kg of CPA or only with vehicle and placed in the less preferred compartment for 25 min. On day 4, the animals were placed in the start compartment and the time spent in each compartment during the 10-min test period was recorded again. The groups treated with 1.0 and 4.0 mg/kg of CPA, spent significantly more time in the compartment in which they experienced the drug effect than the group treated with vehicle. On the other hand, the group treated with 0.4 mg/kg spent significantly less time in the drug-paired compartment. The results indicate a biphasic effect of CPA. Considering that there is evidence that low doses of CPA can also block H3-receptors, we suggest that in goldfish the histaminergic neural system has an inhibitory role in the reinforcing process.