Ventral tegmentum

French ED, Dillon K, Wu X Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra. Neuroreport 8 649—632, 1997 Fujinaga M, Maze M Neurobiology of nitrous oxide-induced antinociceptive effects. Mol Neurobiol 25 167-189, 2002... 

D2 Mostly in striatum, nucleus accumbens and olfactory tubercle but also on neuron cell bodies in substantia nigra and ventral tegmentum where they are the autoreceptors for locally (dendritic) released DA. The loss of specific D2 antagonist binding in the striatum after lesions of the afferent nigro-striatal tract indicates their presynaptic autoreceptor role on terminals there. Other lesion studies have also established D2 receptors on other inputs such as the cortico striatal tract. 

Fiorino, DF, Coury, A, Fibiger, HC and Phillips, AG (1993) Electrical stimulation of reward sites in the ventral tegmentum area increases dopamine transmission in the nucleus acumbers of the rat. Behav. Brain Res. 55 131-141. 

This peptide itself has no selectivity for the two CCK receptors, CCK-A and B, which have so far been established to stimulate IP3/DAG while, like substance P, can close potassium channels to increase neuronal activity. The CCK-B receptor is thought to predominate in the CNS but species differences may make this interpretation difficult. It has a wide distribution in the CNS but is also found in the gut whereas the CCK-A receptor is more restricted but is found in the hypothalamus, hippocampus and in the brainstem. There are high levels of the natural peptide, CCK-8 in cortex, hippocampus, hypothalamus, ventral tegmentum, substantia nigra, brainstem and spinal cord. CCK is one of the most abundant peptides in the brain and CCK co-exists with dopamine, substance P, 5-HT and vasopressin. Interestingly, in the dopamine areas, CCK co-exists in the mesolimbic pathways but in the nigrostriatal projections, the peptide and... 

There is some loss (40-60%) of DA in the nucleus accumbens of the mesolimbic system in the ventral tegmentum (AlO) and cortex at post-mortem but nowhere is it as marked as in the striatum. Some loss of NA, 5-HT, CCK and the enkephalins and of the markers GAD and ChAT (for GABA and ACh) have been reported in the striatum, SN and other areas but these rarely exceed 50% and could be secondary to DA loss. 

The mesolimbic from the ventral tegmentum (VTA, AlO) to the nucleus accumbens, olfactory tubercule, amygdala and pyriform cortex... 

Mesocortical A neural pathway that connects the ventral tegmentum to the cortex, particularly the frontal lobes. It is one of the major dopamine pathways in the brain. 

Historically, stimulants that increase the activity of catecholamines are the oldest drugs in this group (Jones et al. 1973). Reduction in DA activity has been related to a reduction in wakefulness lesions of DA cell groups in the ventral tegmentum that project to the forebrain have been shown to induce a marked reduction in behavioral arousal in rats (Jones et al. 1973), and patients with Parkinson s disease, who exhibit consistent DA lesions, experience severe sleep disorders (Rye and Jankovic 2002). 

Rosin A., Lindholm S., Franck J., Georgieva J. Downregulation of kappa opioid receptor mRNA levels by chronic ethanol and repetitive cocaine in rat ventral tegmentum and nucleus accumbens. Neurosci. Lett. 275 1, 1999. 

Midbrain (ventral tegmentum) Neuronal synapse Cerebral mesolimbic and mesocortical neuronal connections... 

CBi receptors are also expressed at low to moderate levels in the nucleus accumbens. Here CBi receptors are found in a pattern reminiscent of the striatum. CBi receptors are expressed on terminals of the glutamatergic prefrontal cortex accumbens pathways (Robbe et al. 2001). They are also present on the accumbens medium spiny neurons. They appear to be absent from the dopaminergic terminals projecting to the accumbens from the ventral tegmentum. Consequently, cannabinoid stimulation of dopamine release in nucleus accumbens (Tanda et al. 1997) appears to be an indirect effect, perhaps mediated by inhibition of GABA release (Szabo et al. 1999,2002). 

Mesolimbic Midbrain ventral tegmentum (At 0 area) Limbic areas (e.g., amygdala, olfactory tubercle, septal nuclei), cingulate gyrus Arousal, memory, stimulus processing, motivational behavior Relief of psychosis... 

The mesolimbic and mesocortical pathways are dopamine-containing neurones that run from an area in the midbrain called the ventral tegmentum to the limbic system and the prefrontal area of the cerebral cortex respectively. These are areas of the brain that are normally involved in behavioural and emotional functions. 

ABBREVIATIONS PLC, phospholipase C IP3, inositol-1,4,5-trisphosphate DAG, diacylglycerol PLD2, phospholipase D AA, arachidonic acid PL A, phospholipase A cAMP, cyclic AMP SA node, sinoatrial node AV node, atrioventricular node HR, heart rate PTX, pertussis toxin VTA, ventral tegmentum area. 

Low levels in CNS periphery predominate mAChRs in dopaminergic neurons of substantia nigra ventral tegmentum area... 

Cheer JE, Kendall DA, Mason R, Marsden CA. Differential cannabinoid-induced electrophysiological effects in rat ventral tegmentum. Neuropharmacology 44, 633-641 (2003). 

---