Gender differences in brain neurotransmitters

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Neurotransmitters are hormone-like molecules that are released by neuron terminals into a microscopic space called the synapse.  Some of these molecules bind to specialized receptors located on the receiving ends,  usually on dendrites (little branches),  of other neurons.   The neurons of the brain use a multitude of different molecules of this sort. Neurotransmitters in the brain have to do with all psychological and behavioral traits.  Indeed,   thinking, feeling and behaving cannot occur without activation and inhibition of neurons,  which in turn cannot communicate with each other without neurotransmitters.   Allow me to make this point more firmly:   the mind is nothing other than the activity of neurons.  Behavior is the direct result of activities of neurons.  Without neurons,  there can be no mind or behavior,  whatsoever.  We saw in the previous chapter that male and female mammals,  and men and women in particular,  differ in their sexual inner life and behavior.   The fundamental mechanisms of neuronal conduction (which is basically electrical) and of synaptic mediation (which is basically chemical) do not seem to differ between the sexes.  However,  both of these cellular activities have different distributions in the brain as a function of gender.   The true picture of sex differences in regional brain distributions of neurotransmitters is probably very complex,  forming a sort of mosaic.  That is the impression one gets from reading the piecemeal findings reported primarily in the rat literature.   Virtually nothing is known about such sex differences in humans,  even though they most probably exist.   But even at a relatively gross level,  which is more readily accessible to research on humans,  there are significant sex differences in neurotransmitter distribution.  For example,  assay of cerebrospinal fluid in patients,  available due to its necessity or utility for medical diagnostic exploration,  argues to the effect that the neurotransmitter dopamine is more concentrated and more active in men than in women.   Brain serotonin, on the other hand, seems to be less present in men than in women, and in male than female rats.  

There seem to be important sex differences in the way gamma-aminobutyric acid  (an inhibitory neurotransmitter) is organized in male and female mammalian brains.  In one study, picrotoxin (2.5 milligrams of the drug per kilogram of body weight), which was subconvulsive in male Wistar rats, was 92% convulsive in female rats. Four milligrams per kilogram of picrotoxin, a dose that did not produce death in the males, was 75% lethal in the females. A similar significant difference to the analogous treatment was obtained in female and male cats. A sex-related difference in the occurrence of convulsions, latency, and death following picrotoxin administration was also present in mice. However, mice responded in an opposite direction to rats and cats. Three milligrams per kilogram of picrotoxin was 100% convulsive and 27% lethal in male mice, while only 40% convulsive and 0% lethal in female mice. The existence of sex-related differences in the response of mice, rats, and cats to administration of picrotoxin might have its origin in the dimorphisms of the gamma-aminobutyric acid  system in these animal species.   Some neurotransmitters consist of molecules used by various systems of the body for purposes other than synaptic transmission.  This is the case for cholecystokinin and substance P.   In one recent investigation, cholecystokinin (CCK) and substance P (SP) concentrations were measured in discrete brain areas of adult male and diestrous female rats. Significant sex differences in CCK concentration were found in the ventromedial hypothalamic area, medial and lateral preoptic area, nucleus of the diagonal band of Broca, ventral tegmental area, entorhinal and in several cortical areas. No sex differences in SP concentrations were observed in any of these areas. However, significant sex differences in SP concentration were found in the amygdala.

The asymmetry of neurotransmitter concentrations in the hemispheres of the brain differs in men and women.   At least one post mortem investigation has shown that men and women differ in hemispheric asymmetry of serotonin.  It is difficult to estimate whether this sex difference could suffice to explain cognitive sex differences.   Ideally,  we would like to establish links between those few verbal abilities which are slightly superior in women,  or those few visuospatial abilities which are slightly superior in men (see chapter 3), and neurotransmitters.  But such studies remain wanting.  Until the recent advent of advanced brain imaging techniques,  those that can target specific neurotransmitter activity,  the investigation of brain neurotransmitters was limited to painful and dangerous extraction of cerebrospinal fluid by means of spinal taps.  Neurotransmitter asymmetry as a function of gender,  as investigated in non-human mammals, is extremely complex.   There have been a multitude of findings of neurotransmitter asymmetries.   However,  these have not been documented at the whole hemisphere level.   Rather,  the typical finding is of a neurotransmitter asymmetry in a given brain area (typically a nucleus,  which is an aggregate of neurons of similar shape).  Also typical,  is the finding of crossed asymmetries of a given neurotransmitter as a function  of sex and intracerebral location.  In other words,  one typically finds more of a given neurotransmitter on the left side in one sex in a given brain nucleus,  and the opposite asymmetry in another nucleus.  So the overall picture that presents itself currently is of a complex mosaic of sex-related neurotransmitter asymmetries.   Whether the human situation will resemble this remains to be proven.  It would indeed seem appropriately cautious to keep in mind that analyses of the chemical physiology of entire hemispheres may give a misleading account of behaviors and inner life that are indeed sex-specific.  One study has found that the right hypothalamus is more important in mediating male sexual behavior,  and the left for female sexual behavior.  There are promising basic data for future investigations of sex differences in neurotransmitter asymmetry.   Indeed,  though sex differences in neurotransmitter asymmetry have not been much investigated,  as far as I know,  in the human,   concentrations of the major ones are asymmetric.   Such asymmetries have been reported for acetylcholine,  gamma-aminobutyric acid, noradrenalin and dopamine.  Evidence for asymmetry of brain serotonin metabolism in humans includes the finding that right hemisphere stroke produces an increase in serotonin receptor binding, which is not found following comparable left hemisphere strokes.  Furthermore,  left but not right hemisphere strokes produce a massive drop in brain noradrenalin.  Unfortunately,  it is not known whether the sexes differ in these respects.  We also know that some of these neurotransmitters have a mutually agonistic action (potentiate each other),  while others have a mutually antagonistic action (inhibit each other).  Serotonin and noradrenalin are antagonists, as are serotonin and dopamine, acetylcholine and dopamine, and gamma-aminobutyric acid and dopamine.   The distribution of these neurotransmitters is multiply asymmetric but forms a global dynamic balance.    One species whose neurotransmitter distributions has been exhaustively mapped using post-mortem assay,  as a function of gender,  is the rat.   It has been found that dopamine is not very sexually dimorphic if at all,  but that serotonin certainly is,  with females showing indicators of significantly higher serotonergic activity throughout the brain.   The brain area where this sex difference seems to be the highest is the hippocampus.   One study systematically assayed several neurotransmitter asymmetries in several brain areas, comparing male and female rats. Neurochemical correlations in the nucleus accumbens and the striatum did not demonstrate any sex difference, but differences were found in neocortex: female rats had significantly greater hemispheric correlations than males for dopamine, 5-hydroxyindoleacetic acid (serotonin), and serotonin turnover (metabolism).   In short,  the male rats had more hemispheric asymmetry overall.