Terminal autoreceptors

Block the inhibitory feedback effect of released DA on terminal autoreceptors. 

Figure 17.4 The effect of neuroleptics on the activity of DA neurons. Although neuroleptics (DA antagonists) are used primarily to inhibit the postsynaptic effects of released DA they also increase the activity of the DA neuron itself since they (1) inhibit the effect of synaptic DA on nerve terminal autoreceptors and so increase DA release (2) block inhibitory DA autoreceptors on the soma of the DA neuron so that they cannot be stimulated by endogenous DA, possibly released from the neuron s own dendrites and (3) facilitate feedback excitation to the DA neuron from those neurons normally inhibited by distally released DA. All the DA receptors involved are D2 (or possibly D3). — Blocked by D2 antagonists (neuroleptics)...

The actions of amphetamine are widespread throughout the brain. Amphetamine s immediate effect is to alter the release of monoamines in a dose-dependent manner that is specific for each monoamine transmitter neuronal system. The net effect of amphetamine on monoamine release is complex, with some mechanisms tending to increase monoamine release (e.g., blockade of reuptake and nonimpulsedependent release), and several mechanisms tending to diminish release (e.g., activation of somatodendritic and terminal autoreceptors). 

FIGURE 5—39- Presynaptic 5HT1D receptors are also a type of autoreceptor, but they are located on the presynaptic axon terminal and are therefore called terminal autoreceptors. 

FIGURE 5—40. Depicted here is the consequence of the 5HT1D terminal autoreceptor being stimulated by serotonin. The terminal autoreceptor of Figure 5—39 is occupied here by 5HT, causing the blockade of 5HT release, as also shown in Fig. 5—41. 

FIGURE 5—42. If a drug blocks a presynaptic 5HT1D terminal autoreceptor, it would promote the release of 5HT by not allowing 5HT to block its own release. Some 5HT1D antagonists are being tested for the treatment of depression. 

Lawrence AJ, Marsden CA. Terminal autoreceptor control of 5-hydroxytryptamine release as measured by in vivo microdialysis in the conscious guinea-pig. J Neu-rochem 1992 58 142-146. 

Sawyer SF, Tepper JM, Young SJ, Groves PM. Antidromic activation of dorsal raphe neurons from neostriatum physiological characterization and effects of terminal autoreceptor activation. Brain Res 1985 332 15-28. 

Kilts CD, Anderson CM, Ely TD, Nishita JK. 1987. Absence of synthesis modulating nerve terminal autoreceptors on mesoamygdaloid and other mesolimbic dopamine neuronal populations. J. Neurosci. 7 3961-75... 

When the autoreceptor is located on the terminal it is termed a terminal autoreceptor... 

The DA autoreceptor at both sites is the D2 receptor similarly, the NA autoreceptor is the 0(2 receptor. With 5-HT neurones the 5-HTia receptor acts as the main somatodendritic autoreceptor but the 5-HTib/id receptor is the terminal autoreceptor. 

Autonomic nerve endings Sympathetic terminals Autoreceptor Heteroreceptor Inhibition of NE release 2A 2C 2B Inhibition of NE release M,M,... 

Parasympathetic terminal Autoreceptor Heteroreceptor Inhibition of ACh release 2A 2C Inhibition of ACh release m,m. 

Fig. 14.4. Typical nerve ending showing the cell body (i.e., somatodendritic) autoreceptors (B) and the terminal autoreceptors (C). Neurotransmitter molecules also are shown (A). Neurotransmitters can interact with cell body autoreceptors (B) to regulate synthesis and with terminal autoreceptors (C) to regulate release. Shown above is a drug molecule blocking the cell body autoreceptor and preventing an interaction with the neurotransmitter.

Although the present data are consistent with the terminal 5-HT autoreceptor in the afore mentioned species being of the 5-HTjd subclass [50], the presence of the mRNA for all the 5-HTi-like receptors in the raph6 nucleus [117] leads to the possibility that other members of this receptor family may be represented as terminal autoreceptors. Indeed the presence of two inhibitory terminal 5-HT autoreceptors in the guinea pig CNS has been postulated on the basis of the apparent pA of metitepine in antagonising the actions of either 5-HT or sumatriptan in frontal cortex slices [118] and as a result of a detailed study of the dose-response relationship of the inhibitory effect of 5-HT, 5-CT and smnatriptan on 5-HT release in cortex slices [119]. 

---