Summary: Sex differences in neurological disorders like Tourette syndrome, schizophrenia, and ADHD may stem from how histamine affects dopamine in the brain. A new mouse study reveals that histamine decreases dopamine in males but increases it in females, with the female response influenced by the estrous cycle.
Researchers also uncovered that the pathways through which histamine regulates dopamine differ between sexes. These findings suggest that personalized treatments targeting histamine receptors by sex could better address dopamine dysregulation in these conditions.
Key Facts:
- Sex-Specific Effects: Histamine decreases dopamine in males but increases it in females.
- Cycle Influence: Female dopamine response to histamine varies with the estrous cycle.
- Treatment Potential: Sex-based targeting of histamine receptors may improve outcomes in TS, ADHD, and schizophrenia.
Source: SfN
Conditions such as Tourette syndrome (TS), schizophrenia, and Attention-Deficit/Hyperactivity Disorder (ADHD) have sex differences with unknown mechanisms.
These sex-specific mechanisms may inform the development of more effective treatments.
In a new Journal of Neuroscience paper, Meghan Van Zandt and Christopher Pittenger used mice to shed light on the mechanisms underlying sex differences in these psychiatric conditions.
Prior to this study, the researchers knew that these neurological disorders are characterized by altered dopamine signaling in the same brain network.
Additionally, human genetic studies implicate a natural compound called histamine in dysregulating dopamine signaling to potentially underlie at least TS.
Thus, Van Zandt and Pittenger examined sex differences in how histamine interacts with dopamine signaling in this brain network.
By manipulating histamine signaling in mice, the researchers discovered that histamine had opposite effects on dopamine levels in males and females: Histamine decreased dopamine in males and increased dopamine in females. In females, this effect was influenced by the estrous cycle.
The researchers also found sex differences in the mechanisms through which histamine regulated dopamine levels.
According to the authors, this study may inform treatment development, suggesting that sex-specific treatments targeting different histamine receptors may effectively correct dopamine signaling in TS, schizophrenia, and ADHD.
About this dopamine and sex differences research news
Author: SfN Media
Source: SfN
Contact: SfN Media – SfN
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Sex Differences in Histamine Regulation of Striatal Dopamine” by Meghan Van Zandt et al. Journal of Neuroscience
Abstract
Sex Differences in Histamine Regulation of Striatal Dopamine
Dopamine modulation of the basal ganglia differs in males and females and is implicated in numerous neuropsychiatric conditions, including some, like Tourette Syndrome (TS) and attention deficit hyperactivity disorder (ADHD), that have marked sex differences in prevalence.
Genetic studies in TS and subsequent work in animals suggest that a loss of histamine may contribute to dysregulation of dopamine.
Motivated by this, we characterized the modulation of striatal dopamine by histamine, using microdialysis, targeted pharmacology, and shRNA knockdown of histamine receptors.
Intracerebroventricular (ICV) histamine reduced striatal dopamine in male mice, replicating previous work. In contrast, and unexpectedly, ICV histamine increased striatal dopamine in females.
ICV or targeted infusion of agonists revealed that the effect in males depends on H2R receptors in the substantia nigra pars compacta (SNc).
Knockdown of H2R in SNc GABAergic neurons abrogated the effect, identifying these cells as a key locus of histamine’s regulation of dopamine in males.
In females, however, H2R had no discernible role; instead, H3R agonists in the striatum increased striatal dopamine.
Strikingly, the effect of histamine on dopamine in females was modulated by the estrous cycle, appearing only in estrus/proestrus, when estrogen levels are high.
These findings confirm the regulation of striatal dopamine by histamine but identify marked sexual differences in and estrous modulation of this effect.
These findings may shed light on the mechanistic underpinnings of sex differences in the striatal circuitry, and in several neuropsychiatric conditions.
