Obtaining food, shelter or water, or finding a mating partner are examples of motivated behaviors, which are essential to preserve the species. The full expression of such behaviors requires a high but optimal arousal state. We tested the idea that tuberomammillary nucleus (TMN) histamine neurons are crucial to generate such motivated arousal, using a model of the appetitive phase of feeding behavior. Hungry rats enticed with food within a wire mesh box showed intense goal-directed motor activity aimed at opening the box, an increase in core temperature, a fast histamine release in the hypothalamus and an early increase in Fos immunoreactivity in TMN and cortical neurons. Enticing with stronger-tasting food induced stronger motor, temperature and Fos immunoreactivity brain responses than ordinary food pellets. TMN lesion greatly decreased all of those responses. We conclude that histamine neurons increase arousal and vegetative activity, allowing the normal unfolding of voluntary, goal-directed behavior such as obtaining food.

The histaminergic system is one component of the ascending arousal system which is involved in wakefulness, neuroendocrine control, cognition, psychiatric disorders and motivation. During the appetitive phase of motivated behaviors the arousal state rises to an optimal level, thus giving proper intensity to the behavior. Previous studies have demonstrated that the histaminergic neurons show an earlier activation during the appetitive phase of feeding, compared to other ascending arousal system nuclei, paralleled with a high increase in arousal state. Lesions restricted to the histaminergic neurons in rats reduced their motivation to get food even after 24h of food deprivation, compared with intact or sham lesioned rats. Taken together, these findings indicate that the histaminergic system is important for appetitive behavior related to feeding. However, its role in other goal-directed behaviors remains unexplored. In the present work, male rats rendered motivated to obtain water, sex, or amphetamine showed an increase in Fos-ir of histaminergic neurons in appetitive behaviors directed to get those reinforcers. However, during appetitive tests to obtain sex, or drug in amphetamine-conditioned rats, Fos expression increased in most other ascending arousal system nuclei, including the orexin neurons in the lateral hypothalamus, dorsal raphe, locus coeruleus and laterodorsal tegmental neurons, but not in the ventral tegmental area, which showed no Fos-ir increase in any of the 3 conditions. Importantly, all these appetitive behaviors were drastically reduced after histaminergic cell-specific lesion, suggesting a critical contribution of histamine on the intensity component of several appetitive behaviors.

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REsuMEnLa lesión o hipofunción vestibular bilateral (HVB) es un cuadro clínico que provoca oscilopsias y desequilibrio incapacitante que se agrava en oscuridad. Algunas de las causas de HVB son el uso de drogas ototóxicas, enfermedad de Ménière bilateral, enfermedades autoinmunes y degeneración espinocerebelar. El manejo de esta discapacidad es complejo y muchas veces la rehabilitación no logra los objetivos deseados. Una de las alternativas terapéuticas futuras para la HVB y aún en plena fase experimental es el implante vestibular, cuyo funcionamiento en términos generales es similar al de un implante coclear. En esta revisión se analiza la génesis e historia del desarrollo de los implantes vestibulares, sus principales características y el futuro de su implementación.Palabras clave: Lesión vestibular bilateral, enfermedad de Ménière, oscilopsias, desequilibrio, ototóxicos, implante vestibular. ABsTRACTBilateral vestibular loss (BVL) is a clinic syndrome that produces oscillopsias and disabling disequilibrium, especially in darkness. Some causes of BVL are the use of ototoxic drugs, bilateral Ménière disease, autoinmune ear disorders and spinocerebellar ataxia. The management of this disability is complex and many times the rehabilitation does not accomplish with the desired goals. One future therapeutic alternative for BVL and still in an experimental stage is the vestibular implant, whose overall functioning is similar to a cochlear implant. In this review we analyze the genesis and history of vestibular implant development, its main technical characteristics and the future of its implementation.