Central Neurochemistry Research Articles

Association between increased retinal background noise and co-occurrent regular cannabis and alcohol use

BackgroundCannabis consumption is widespread across the world, and the co-occurrence of cannabis use and alcohol consumption is common. The study of background noise - resting-state neural activity, in the absence of stimulation - is an approach that could enable the neurotoxicity of these substances to be explored. Preliminary results have shown that delta-9-tetrahydrocannabinol (Δ9-THC) causes an increase in neural noise in the brain. Neurons in the brain and the retina share a neurotransmission system and have similar anatomical and functional properties. Retinal function, evaluated using an electroretinogram (ERG), may therefore reflect central neurochemistry. This study analyses retinal background noise in a population of regular co-occurrent cannabis and alcohol consumers. MethodsWe recorded the flash ERGs of 26 healthy controls and 45 regular cannabis consumers, separated into two groups based on their alcohol consumption: less than or equal to 4 glasses per week (CU ≤ 4) or strictly >4 glasses per week (CU >4). In order to extract the background noise, the Fourier transform of the pseudo-periodic and sinusoidal signals of the 3.0 flicker-response sequence was calculated. This sequence represents the vertical transmission of the signal from cones to bipolar cells. The magnitude of the background noise is defined as the average of the magnitudes of the two neighbouring harmonics: harmonic −1 (low frequency noise) and harmonic +1 (high frequency noise). ResultsThe magnitude of harmonic −1 was significantly increased between the groups CU > 4 (6.78 (±1.24)) and CU ≤ 4 (5.69 (±1.80)) among regular users of cannabis and alcohol. A significant increase in the average magnitude of the two harmonics was found between the groups CU > 4 (5.12 (±0.92)) and CU ≤ 4 (4.36 (±1.14)). No significant difference was observed with regard to the magnitude of the harmonic +1. ConclusionsThe increase in background noise may reflect the neurotoxicity of cannabis, potentiated by alcohol consumption, on retinal neurons dynamic. This neural disruption of the response generated by retinal stimulation may be attributable to altered neurotransmitter release.

The Neurobiology Shaping Affective Touch: Expectation, Motivation, and Meaning in the Multisensory Context.

Inter-individual touch can be a desirable reward that can both relieve negative affect and evoke strong feelings of pleasure. However, if other sensory cues indicate it is undesirable to interact with the toucher, the affective experience of the same touch may be flipped to disgust. While a broad literature has addressed, on one hand the neurophysiological basis of ascending touch pathways, and on the other hand the central neurochemistry involved in touch behaviors, investigations of how external context and internal state shapes the hedonic value of touch have only recently emerged. Here, we review the psychological and neurobiological mechanisms responsible for the integration of tactile “bottom–up” stimuli and “top–down” information into affective touch experiences. We highlight the reciprocal influences between gentle touch and contextual information, and consider how, and at which levels of neural processing, top-down influences may modulate ascending touch signals. Finally, we discuss the central neurochemistry, specifically the μ-opioids and oxytocin systems, involved in affective touch processing, and how the functions of these neurotransmitters largely depend on the context and motivational state of the individual.

Cerebrospinal Fluid Inflammatory Cytokines and Aggression in Personality Disordered Subjects

Background:Neurochemical studies have pointed to a modulatory role in human aggression for a variety of central neurotransmitters and neuromodulators such as cytokines. While animal studies of cytokines suggest an aggression-facilitating role for central cytokines, especially for interleukin-1β and other cytokines, no cerebrospinal fluid studies of cytokines have yet been reported in regard to human aggression.Methods:Basal lumbar cerebrospinal fluid samples were obtained from 38 physically healthy subjects with DSM-5 Personality Disorder and assayed for cerebrospinal fluid interleukin-6 (log IL-6) and cerebrospinal fluid soluble IL-1 Receptor II protein in the context of their relationship with measures of aggression.Results:Cerebrospinal fluid soluble interleukin-1 Receptor II (r=.35, r2 = .12, P= .03), but not log interleukin-6 (r = -.05, r2 = .00, P= .76), levels were positively correlated with a composite measure of aggression. Adding relevant covariates, including cerebrospinal fluid levels of serotonin and dopamine metabolites, to the statistical model doubled the strength of this relationship (partial r = .54, r2 = .29, P= .002). No relationship was seen with history of suicidal behavior or with any measure of impulsivity, negative affectivity, or of general dimensions of personality.Conclusion:These data suggest a positive relationship between at least one inflammatory cytokine in the central nervous system and aggression in human subjects. This finding adds to the complex picture of the central neurochemistry of impulsive aggression in human subjects.

Differential visceral nociceptive, behavioural and neurochemical responses to an immune challenge in the stress-sensitive Wistar Kyoto rat strain

A highly regulated crosstalk exists between the immune and neuroendocrine systems with the altered immune responses in stress-related disorders being a valid example of this interaction. The Wister Kyoto (WKY) rat is an animal model with a genetic predisposition towards an exaggerated stress response and is used to study disorders such as depression and irritable bowel syndrome (IBS), where stress plays a substantial role. The impact of a lipopolysaccride (LPS) immune challenge has not yet been investigated in this animal model to date. Hence our aim was to assess if the stress susceptible genetic background of the WKY rat was associated with a differential response to an acute immune challenge. Central and peripheral parameters previously shown to be altered by LPS administration were assessed. Under baseline conditions, WKY rats displayed visceral hypersensitivity compared to Sprague Dawley (SD) control rats. However, only SD rats showed an increase in visceral sensitivity following endotoxin administration. The peripheral immune response to the LPS was similar in both strains whilst the central neurochemistry was blunted in the WKY rats. Sickness behaviour was also abrogated in the WKY rats. Taken together, these data indicate that the genetic background of the WKY rat mitigates the response to infection centrally, but not peripherally. This implies that heightened stress-susceptibility in vulnerable populations may compromise the coordinated CNS response to peripheral immune activation.

The microbiome-gut-brain axis: from bowel to behavior

The ability of gut microbiota to communicate with the brain and thus modulate behavior is emerging as an exciting concept in health and disease. The enteric microbiota interacts with the host to form essential relationships that govern homeostasis. Despite the unique enteric bacterial fingerprint of each individual, there appears to be a certain balance that confers health benefits. It is, therefore, reasonable to note that a decrease in the desirable gastrointestinal bacteria will lead to deterioration in gastrointestinal, neuroendocrine or immune relationships and ultimately disease. Therefore, studies focusing on the impact of enteric microbiota on the host and in particular on the central nervous system are essential to our understanding of the influence of this system. Recent studies published in this Journal demonstrate that germ-free mice display alterations in stress-responsivity, central neurochemistry and behavior indicative of a reduction in anxiety in comparison to conventional mice. Such data offer the enticing proposition that specific modulation of the enteric microbiota may be a useful strategy for stress-related disorders and for modulating the co-morbid aspects of gastrointestinal disorders such as irritable bowel syndrome and inflammatory bowel disease.

Activation of Central Biogenic Amines Following Aggressive Interaction in Male Lizards, <i>Anolis carolinensis</i>

Many stimuli, including social aggression, activate endocrine stress mechanisms, presumably mediated or modulated by central neurotransmitters. To determine the effects of aggression on central neurochemistry, reproductively active male Anolis carolinensis were paired and allowed to establish social dominance relationships. While combatants cohabited, the fight losers invariably became socially subordinate and displayed darker color, selection of lower perch sites, and lower body posture than the winners. After one hour, one day, one week, or one month of cohabitation animals were sacrificed. Each member of a pair was killed at approximately the same time, along with animals kept isolated as controls. Diencephalon, non-optic lobe midbrain and hindbrain were analyzed for indoleamines, catecholamines and metabolites by coulochem electrode array HPLC. Early activation (by one hour) of the serotonergic system in subordinate male lizards was indicated by decreased serotonin (5-HT), increased 5-hydroxy-indoleacetic acid (5-HIAA) levels and 5-HIAA/5-HT ratio. Substrate 5-hydroxy-tryptophan (5-HTP) also increased in losing males, suggesting enhanced production as well as turnover. Significant 5-HTP and 5-HIAA/5-HT increases for subordinate males, compared with levels in control and dominant males, were greatest at one hour and diminished thereafter. This pattern of indoleamine system activation is consistent with stress-induced stimulation of the serotonergic system and prolonged activation of the stress response in subordinate animals, as well as serotonergic inhibition of aggression. In contrast with serotonin, subordinate males did not have increased catecholamine system activation following one hour of interaction. The ratio of DOPAC/dopamine was lower following one hour of interaction in subordinate males. Adrenergic system activation, indicated by metanephrine/epinephrine ratio, increased with time in losing males, except that after one month of cohabitation, turnover returned to levels that equaled those of control animals. Noradrenergic metabolite MHPG, as well as MHPG/NE ratio, were significantly reduced in dominant males at one hour and one week. Changes in adrenergic system activation, not seen in or registered by noradrenergic systems, indicate a possible role for central epinephrine in social stress accommodation.