Neurotransmitter Receptor Alterations

One of the most consistent findings in precfinical studies of anddepressant treatments (including electroconvulsive shock) 

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The cellular consequences of neurotransmission can be both short term (acute) and long term (chronic). Acutely, stimulation of neurotransmitter receptors alters levels of intracellular signaling molecules, which may induce the neuron to fire or alter the responsiveness of the neuron to further stimulation. Over time, the persistent activation of receptors that occurs with... 

The neurotransmitter receptor hypothesis suggests that depression is related to abnormal functioning of neurotransmitter receptors. In this model, antidepressants presumably exert therapeutic effects by altering receptor sensitivity. In fact,... 

The ability of morphine to desensitize other neurotransmitter receptors coupled to K+ channels may cause long-term consequences in the activity of neurons. The uncoupling of K+ channel from non-opioid receptors that normally tonically inhibit cell firing could result in an increase in the basal firing of the cells. Changes in the set point of neuronal firing could influence gene expression in the cells and alter the molecular properties of the neurons. 

Other drugs, like GHB and Rohypnol , can interact directly with the neurotransmitter receptors to either enhance or block the effects of the brain s own neurotransmitters. Still other drugs can alter the metabolic breakdown or clearance of certain neurotransmitters after they are released from the synaptic terminal, thereby altering how long the neurotransmitter affects the activity of other nearby neurons. 

In the last decade, considerable evidence has emerged that certain steroids may alter neuronal excitability via their action at the cell surface through interaction with certain neurotransmitter receptors. For steroids with these particular properties, the term neuroactive steroids has been used (Majewska et al. 1986 Paul and Purdy 1992 Rupprecht and Holsboer 1999). 

In my admittedly biased view, the most coherent approach is that of a profoundly disturbed stress system that under specific conditions paves the way to development of mood disorders. These stress-system alterations can be genetic or acquired through trauma in early life or even in utero. Consistent with this neuroendocrine hypothesis are findings that centrally released neuropeptides that drive the HPA system also have behavioral effects that are similar to affective symptoms. This view is further supported by the documented ability of various antidepressants to enhance corticosteroid receptor synthesis and efficacy. Moreover, the stress system, particularly the corticosteroids and their receptors, interferes with all of the neurotransmitter receptor systems, including intracellular signaling, that have been considered in the context of mood disorders. New drugs targeted directly to various elements of the stress system will constitute a major step forward. 

Kendall DA, Stancel GM, Enna SJ The influence of sex hormones on antidepressant-induced alterations in neurotransmitter receptor binding. J Neurosci 2 354-360, 1981... 

When two different receptor sites utilizing different neurotransmitters are arranged so as to influence a single receptor, there is generally considered to be a primary neurotransmitter receptor site, which influences its receptor in the usual manner (i.e., it turns on a second messenger or alters an ion channel). In this example, furthermore, there is a second receptor site, which can influence the receptor generally only when the primary neurotransmitter is binding at the primary receptor... 

FIGURE 7—22. The mechanism of action of lithium is not well understood but is hypothesized to involve modifying second messenger systems. One possibility is that lithium alters G proteins and their ability to transduce signals inside the cell once the neurotransmitter receptor is occupied by the neurotransmitter. Another theory is that lithium alters enzymes that interact with the second-messenger system, such as inositol monophosphatase, or others. 

Alterations of Neurotransmitter Receptors in Schizophrenia Evidence from Postmortem Studies... 

Alterations of neurotransmitter receptors in schizophrenia evidence from postmortem studies... 

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