Prefrontal activity decline in women under a single dose of diazepam during rule-guided responses: an fMRI study

Abstract

Daily life events confront us with new situations demanding responses to usual and unusual rules. Diazepam (DZ), a clinically important drug, facilitates the inhibitory activity of the GABAergic system. Prefrontal cortex, rich in DZ receptors, coordinates necessary resources to direct actions according to rules. The balance between excitatory and inhibitory activity is critical to achieve optimal function of brain systems leading to complex functions. Major sex differences in the physiological mechanisms of the GABAergic system have been reported. However, the differential influence of DZ on men and women in neural activity during behavior directed by frontal lobes remains unexplored. The ability of healthy volunteers to select responses following usual/congruent and novel/incongruent rules, and brain correlates were measured with fMRI under the administration of DZ and a placebo. 10 mg of DZ was enough to decrease the performance in a different manner between men and women. While reaction times increased in both men and women, women committed more errors selecting responses than men under DZ. Men demonstrated increased activity, while women demonstrated decreased activity in frontal regions involved in response selection of rules. These findings could have important consequences in understanding the differential influences of DZ between the sexes in complex daily life situations. More importantly, this study emphasizes the importance of understanding the differential effects on men and women of drugs widely employed by society, thereby achieves better therapeutic results and avoids side effects that the present study revealed to be different between sexes.

Neurochemistry of response inhibition and interference in gambling disorder: a preliminary study of γ-aminobutyric acid (GABA+) and glutamate–glutamine (Glx)

“…In contrast to the Flanker task, response times in the SST did not depend on gambling status, but the positive correlations between Go error response times and dACC GABA+/Cr and the GABA+/Glx ratio indicated GD-specific abnormalities. Previous research with non-gambling populations showed that enhancing GABA levels via agonists, such as Diazepam or Lorazepam, prolongs response times across tasks 38,68 , like the positive association between baseline GABA+/Cr and SST response times found in the current investigation. While GABA agonists induce widespread increases in cortical GABA, our investigation found the relationship between GABA+/Cr and response times significant within the dACC voxel.…”

Effects of footshock stress on social behavior and neuronal activation in the medial prefrontal cortex and amygdala of male and female mice

“…Tan et al obtained comparable results in the mPFC of females after chronic adolescent social isolation stress, with pyramidal neurons being less activated during sociability tests [ 39 ]. Alprazolam significantly lowered the number of cFos+ cells in the IL compared to vehicle-injected female controls, consistent with the benzodiazepine effects observed in humans: women demonstrate decreased activity in frontal regions after treatment, while an opposite effect is present in males [ 40 ]. This effect could be related to females having significantly higher GABA-A benzodiazepine receptor availability [ 41 ].…”

Effects of footshock stress on social behavior and neuronal activation in the medial prefrontal cortex and amygdala of male and female mice

“…Sex differences in the modulation of social behavior by the mPFC were previously explored regarding oxytocin-receptor-expressing interneurons which have differential responses to oxytocin in male and female mice and regulate the social motivation of female mice to interact with male mice during estrus [37]. Alprazolam significantly lowered the number of cFos+ cells in the IL compared to vehicle-injected female controls, consistent with the benzodiazepine effects observed in humans: women demonstrate decreased activity in frontal regions after treatment, while an opposite effect is present in males [38]. This effect could be related to females having significantly higher GABA-A benzodiazepine receptor availability [39].…”