Table 2.

Selected neurochemical sex differences in the brain.

Neurochemical system/pathway	Known roles	Species	Selected sex differences
Cathecolamines (also see Figure 1)	Involved in the control of a variety of processes including reproduction and sexual behavior [51; 52], respiration [53], and stress responses [54].	Rat	Male have higher norepinephrine (NE) levels in the amygdala and hypothalamus at day 25. Direction of this sex difference is reversed at day 300 [62].
			In response to chronic physical stress, dopamine (DA) activity is upregulated only in males whereas NE activity is increased only in females [58].
		Human	Women appear to be more dependent than men on NE for long-term emotional memory formation [63].
Serotonin	Modulates a wide variety of processes including mood, aggression, perception, reward, and attention [64].	Rat and human	Sex differences in the serotonergic system are found at multiple levels [65; 66; 67; 68; 69]. See Figure 2 for an illustration of some of these differences.
Aromatase	Plays a key role in sexual differentiation of the brain by converting testosterone to 17β-estradiol[70].	Rat	Aromatase activity is higher in males than females in many regions including the anterior hypothalamus, BNST and POA [71].
			Only males experience spikes in the expression of brain-specific and total aromatase during embryonic development and shortly after [72].
Vasopressin (VP)	VP in the central nervous system (CNS) has been linked to learning, memory and motor behavior [73]. It has also been connected to the control of social behaviors such as pair-bonding, parenting and aggression [74].	Rat	The number of vasopressin-positive cells is 2 to 3 times higher in males than in females [75].
			Vasopressin-positive projections are also 2 to 3 times denser in males [75].
			Intrahypothalamic release of VP due to an increase of plasma osmolality is higher in females. [76]
		Human	Some studies have found that plasma VP concentrations are higher in men than in women [73].
Cholinergic system	The cholinergic system helps regulate the sleep-wake cycle and modulates synaptic plasticity implicated in memory, learning, and development [77; 78]. Sex differences are found at many points in the cholinergic system [reviewed in 73].	Rat	Levels of acetylcholine (ACh) are higher in females, regardless of estrous cycle, than in males [79]. The maximal level of Ach in females was found at proestrus.
			The binding affinity of muscarinic Ach receptors is lower in females than in males [80]. Estrogens appear to modulate the binding activity of these receptors [81].
		Human	Men are more sensitive to cholinergic stimulation than women [82].
Opioid system	Opioids are a class of chemical for which receptors are found throughout the CNS [83; 84]. Opioids exert an analgesic effect and also play a role in stress response and reproduction [85].	Rat and mouse	Generally, μ and κ class opioids seem more effective in males than females although in some cases the effectiveness is equal [86]. In a minority of cases, they are more effective in females.
		Human	μ-opioids appear more effective in women than in men [86].
			μ-opioids show significantly higher binding potential in women in the amygdala, thalamus and the cerebellum [87]. The sex difference in the first two regions is reversed after menopause.