Midbrain

Liss B, Haeckel O, Wildmann J et al (2005) K-ATP channels promote tire differential degeneration of dopaminergic midbrain neurons. Nat Neurosci 8 1742-1751... 

Both psychostimulants D-amphetamine and cocaine elevate extracellular dopamine concentrations in the terminal region of midbrain dopamine neurons,... 

Multiple sclerosis (MS) 4. In rats with EAE, an animal model of multiple sclerosis, AEA and 2-AG levels are decreased in the striatum and midbrain. This might be associated with motor impairment 4. Inhibitors of degradation (both FAAH and cellular re-uptake)... 

The neuraxis is the rostrocaudal extension of the nervous system including forebrain, midbrain, brainstem, spinal cord, and peripheral nerves. 

Major efferent projections of the hypothalamic orexin system comprise descending and ascending, dorsal and ventral pathways that terminate preferentially in aminergic, endocrine, and autonomic control centers in the hypothalamus, midbrain, brainstem, and spinal cord, as well as in limbic cortical and subcortical structures, including sqDtum, amygdala, thalamus,... 

Afferent input from cutaneous and visceral nociceptors is known to converge on spinal neurons, which accounts for the referral of pain between visceral and cutaneous structures (e.g. cardiac pain gets referred to the chest and left upper arm in patients suffering from angina pectoris). Projection neurons in the spinal dorsal horn project to cell nuclei in supraspinal areas such as the thalamus, brainstem and midbrain. Of these, the synaptic junctions in the thalamus play a very important role in the integration and modulation of spinal nociceptive and non-nociceptive inputs. Nociceptive inputs are finally conducted to the cortex where the sensation of pain is perceived (Fig. 1). The mechanisms via which the cortex processes nociceptive inputs are only poorly understood. 

Several classes of drugs modulate the firing rates or patterns of midbrain dopamine neurons by direct, monosynaptic, or indirect, polysynaptic, inputs to the cell bodies within the ventral mesencephalon (i.e., nicotine and opiates). In contrast, amphetamine, cocaine, and methylphenidate act at the level of the dopamine terminal interfering with normal processes of transmitter packaging, release, reuptake, and metabolism. 

Carlezon WA Jr, Nestler EJ Elevated levels of GluRl in the midbrain a trigger for sensitization to drugs of abuse Trends Neurosci 25 610—615, 2002... 

D4 Again very few in number compared with D2 but located in frontal cortex, midbrain and amygdala. High affinity for DA (Alj 20 nM) and a number of variants in humans. 

The best-understood sites of action of morphine are at spinal and brainstem/ midbrain loci, producing both the wanted and unwanted effects of the opioid. The spinal actions of opioids and their mechanisms of analgesia involve (1) reduced transmitter release from nociceptive C-fibres so that spinal neurons are less excited by incoming painful messages, and (2) postsynaptic inhibitions of neurons conveying information from the spinal cord to the brain. This dual action of opioids can result in a... 

Chiodi, LA and Bunney, BS (1983) Typical and at q)ical neuroleptics differential effects of chronic administration on the activity of A9 and AlO midbrain dopamine neurones. J. Neurosci. 3 1607-1619. 

There are other important sites of opiate actions located in the 5-HT and noradrenergic nuclei of the brainstem and midbrain including the raphe nuclei, the periaquaductal... 

Finally, as outlined above, descending monoamine systems, originating in the midbrain and brainstem that act through the spinal release of noradrenaline and 5-HT, modulate the spinal transmission of pain. Alphai adrenoceptors appear to be important in this role but it is unlikely that behavioural effects such as sedation can be separated from the analgesia. Since both noradrenaline and 5-HT are key transmitters in the control of mood and anxiety and yet also participate in the control of sensory events that lead to... 

Figure 22.5 Pathways involved in cortico-thalamic synchrony and EEG arousal. The ascending reticular activating system (ARAS) extends from the cephalic medulla through the pons and midbrain to the thalamus (see Moruzzi and Mayoun 1949). It is activated by impulses in collaterals of the spinothalamic sensory pathway running to specific thalamic nuclei (SpThNc) and in turn activates much of the cortex, partly through the non-specific thalamic nuclei (NspThNc), which also receive inputs from SpThNc and also via the nucleus basalis (NcB). Its stimulation is followed by EEG arousal. It is probable that reciprocal links between cortical areas and the thalamus, particularly NspThN, lead to slow-wave (8 Hz) cortical EEG synchrony and, in the absence of appropriate sensory input and ARAS activity, a sleep state...

The motor activation produced by psychomotor stimulants has been long associated with the midbrain dopamine systems. While focused stereotyped behavior produced by high doses of indirect sympathomimetics is blocked by removal of dopamine terminals in the corpus striatum (Creese and Iversen 1975), the locomotor activation produced by low doses of indirect sympathomimetics is blocked by removal of dopamine terminals in the region of the nucleus accumbens (Kelly et al. 1975). This dopaminergic substrate for psychostimulant effects appears selective for the indirect sympathomimetics in that dopamine lesions to the region of the nucleus... 

Fuxe 1965) and throughout the brain stem and spinal cord. A series of studies employing small intracerebral lesions (Anden et al. 1966 Ungerstedt 1971) indicated that most 5-HT nerve terminals in the forebrain arise from raphe nuclei in the midbrain and that the axons ascend through the lateral hypothalamus within the medial forebrain bundle (Moore and Heller 1967 Azmitia 1978 Conrad et al. 1974). 

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