Gender differences in brain neurotransmitters
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.
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