The Histaminergic Tuberomamillary Nucleus Is Involved in Appetite for Sex, Water and Amphetamine

Abstract

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.

Histaminergic Neurotransmission as a Gateway for the Cognitive Effect of Oleoylethanolamide in Contextual Fear Conditioning

“…Good memory consolidation of fear tasks requires emotional arousal and the engagement of the basolateral amygdala (BLA) ( Izquierdo et al, 2016 ). Emotionally relevant experiences activate the histaminergic system ( Contreras et al, 2016 ) that is crucial for the consolidation, retrieval, and extinction of such memories with different anatomical and temporal patterns ( Fiorenza et al, 2012 ; Benetti et al, 2015 ; Fabbri et al, 2016 ). In particular, activation of histamine H 1 or H 2 receptors in the BLA (but also in the hippocampus, infralimbic, and ventromedial prefrontal corteces) facilitates memory consolidation of inhibitory avoidance and contextual fear conditioning, whereas their specific antagonists have an opposite effect in the consolidation of different tasks ( Cangioli et al, 2002 ; Giovannini et al, 2003; Silva et al, 2006 ; Benetti and Izquierdo 2013 ).…”

Neuronal histamine and the memory of emotionally salient events

“…The brain histaminergic system is likely involved in emotionally ‘appetitive’ behaviours as well. The histaminergic system is important for appetitive behaviour related to feeding (Valdés et al, 2010) and other goal‐directed behaviours, as observed in rats motivated to obtain sex, amphetamine or drinking water (Contreras et al, 2016). The authors suggested that histamine critically contributes to the intensity component of several appetitive behaviours.…”

Central Effects of 3-Iodothyronamine Reveal a Novel Role for Mitochondrial Monoamine Oxidases

“…Histamine in the brain accumulates in mast cells, astrocytes ( 23 ), and in the few histaminergic neurons that are concentrated in the hypothalamus from which they project to most of the brain areas including the hippocampus and cortex ( 24 ). Neuronal histamine is implicated in memory, control of the sleep/wake cycle, feeding, thermoregulation, motility, and it is considered an endogenous neuroprotective mediator against excitotoxicity ( 25 , 26 ). Histamine in the brain is mainly degraded by N -methyl transferase producing N -methylhistamine ( 27 ) which is, in turn, a good substrate for MAO-B.…”