Limbic areas

Autoradiography and receptor mRNA studies have shown Hi receptors to be located in most of the brain areas innervated by the ascending histaminergic axons, e.g. cerebral cortex, hippocampus, limbic areas and hypothalamus. Their presence in the cerebellum is not accompanied by appropriate histaminergic innervation. Very few are found in the striatum but this region does show a high density of H2 receptors. H2 receptors are also found with Hi in the cortex, hippocampus and limbic areas, but not in the hypothalamus. Although basically presynaptic the H3 receptor is also found postsynaptically in the striatum and cerebral cortex (Pollard et al. 1993). 

Staley J.K., Rothman R.B., Rice K.C., Partilla J., Mash D.C. Kappa2 opioid receptors in limbic areas of the human brain are upregulated by cocaine in fatal overdose victims. J. Neurosci. 17 8225, 1997. 

A role for the 5-HT7 receptor in the regulation of circadian rhythms has been implicated. As discussed above, 5-HT has been known for some time to induce phase shifts in behavioral circadian rhythms and modulate neuronal activity in the suprachiasmatic nucleus, the likely site of the mammalian circadian clock. The pharmacological characteristics of the effect of 5-HT on circadian rhythms are consistent with 5-HT7 receptor. Moreover, mRNA for the 5-HT7 receptor is found in the suprachiasmatic nucleus. There is also increasing evidence that the 5-HT7 receptor may play a role in psychiatric disorders. The regional distribution of 5-HT7 receptors in brain includes limbic areas and cortex. Atypical antipsychotics, such as clozapine and risperidone, and some antidepressants display high affinity for this receptor. In the periphery, 5-HT7 receptors havebeenshown to mediate relaxation of vascular smooth muscle. 

Hippocampus, septum, amygdala, cortical limbic area Agonists buspirone, gepirone, ipsapirone, flesinoxan Antagonists WAY 100135, BMY7378, NAN-190 Possible clinical use of agonists anxiolytics, antidepressants 5-HTi receptors... 

In essence, all of the older benzodiazepines that are structurally related to chlordiazepoxide and diazepam are termed 1,4-benzodiazepines. The chemical structure of some commonly used benzodiazepines is shown in Figure 9.2. They enhance the actions of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. As a consequence, they affect the activities of the cerebellum (concerned with balance and coordination), the limbic areas of the brain and the cerebral cortex (thought and decision making, fine movement control). 

The psychological effects of cannabis are due to cannabinoids such as A -tetrahydrocannabinol (THC) which interact with specific cannabinoid receptors in the brain (Devane et al.,1988 Matsuda et al., 1990). The functions of these receptors are not known but high concentrations are present in sensory and limbic areas, and THC also increases dopamine release from the nucleus accumbens and frontal cortex (Tanda et al., 1987) and decreases the release of acetylcholine (Trzepacz, 2000). 

Another approach considers the effects of various ligands on their receptors located in the diencephalic and mesiotemporal areas. Cell clusters in the hypothalamus coordinate the normal regulation of the vegetative functions of sleep, appetite, and sexual drive, which are typically disrupted in severe depression. In addition, the limbic area modulates many aspects of behavior and mood that are characteristically disturbed in affective disorders. 

The Davidson hypothesis is complex because it has not just two but four components the left vs. the right and top (cortex) vs. the bottom (limbic areas). Oversimplifying for the sake of clarity, preferential activation of the left prefrontal area is associated with positive dispositional affects like affections and optimism, whereas preferential activation of the right prefrontal area is associated with negative dispositional affects like social fearfulness and pessimism. 

How and why is the limbic forebrain selectively activated in REM so as to produce this kind of affective experience The how answer is that in addition to its major cholinergic innervation from the basal forebrain the limbic area receives a direct projection from the dorsolateral pontine tegmentum, where the cholinergic neurons that become selectively active in REM sleep are found in animals. PET studies can t yet tell us if this particular brain stem region is selectively activated in human REM sleep, but we hypothesize that such a homology is likely. 

FIGURE 5-54. Serotonergic projections from raphe to limbic areas may be involved in anxiety and panic. 

The mesolimbic dopamine pathway projects from dopaminergic cell bodies in the ventral tegmental area of the brainstem to axon terminals in limbic areas of the brain, such as the nucleus accumbens (Fig. 10—8). This pathway is thought to have an important role in emotional behaviors, especially auditory hallucinations but also delusions and thought disorder (Fig. 10—9)-... 

The D3 and D4 receptors appear to be largely restricted to the limbic areas of the rat and human brain. These receptors are of particular interest as they have a high affinity for such atypical neuroleptics as clozapine. Such... 

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