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Mental disorders
Depression and Manic Depression
Alzheimer’s-type Dementia

Help Adrenergic and noradrenergic systems in panic/anxiety Antianxiety Sédatifs, anxiolytiques, hypnotiques
Anxiolytic drug targets: beyond the usual suspects Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype Identification of Calcineurin as a Key Signal in the Extinction of Fear Memory
Facilitation of Conditioned Fear Extinction by Systemic Administration or Intra-Amygdala Infusions of D-Cycloserine as Assessed with Fear-Potentiated Startle in Rats Imaging the GABA-benzodiazepine receptor subtype containing the alpha5-subunit in vivo with [11C]Ro15 4513 positron emission tomography

In addition to benzodiazepines, antidepressants, and neuroleptics, certain antihistamines (such as hydroxyzine) have sedative properties and are used to treat certain relatively short-term forms of anxiety.

Some serotonergic
5-HT1A receptor agonists, such as buspirone, by activating the serotonergic autoreceptors, reduce the secretion of serotonin, thus producing an anxiolytic effect comparable to that of medications which activate GABA receptors, such as benzodiazepines.

The fact that certain serotonin-reuptake-inhibiting antidepressants (substances such as fluvoxamine, which increase the secretion of serotonin) can be used to treat obsessive-compulsive disorder shows at least two things. First, the amount of a neurotransmitter is too vague a criterion to account on its own for all of the complex phenomena involved in anxiety disorders. Second, anxiety and depression probably involve some similar biological mechanisms. For example, we know that people who have anxiety disorders in childhood are at greater risk for developing depression later in life.

Link : Anxiety and the Serotonin Receptor Link : Serotonergic system and panic/anxiety




Tranquilizers should not be prescribed automatically whenever anxiety symptoms are present, because these symptoms are not considered pathological unless they become disabling for the person experiencing them. At that point, they warrant specific treatment, most often with benzodiazepines, which can be prescribed temporarily without any significant negative health effects. In such cases, benzodiazepines can generally effectively reduce the anxiety that the person is experiencing, but they cannot attack its underlying causes.

The term “benzodiazepine” refers to the general class of chemicals to which these molecules belong. Each member of this class has a generic name or is simply known by its trade name. The following table lists some of the most common benzodiazepines.

Generic name (active ingredient)   Marketed under the trade name(s):
Diazepam   Valium, Vivol, T-Quil, Valrelease
Lorazepam   Ativan, Alzapam, Loraz
Alprazolam   Xanax, Alprazolam Intensol
Chlordiazepoxide   Librium, Novopoxide, Libritabs
Flurazepam   Dalmane, Novoflupam, Somnol
Nitrazepam   Mogadon
Triazolam   Halcion
Temazepam   Restoril
Oxazepam   Serax

Researchers have long known that benzodiazepines bind to GABA-A receptors, thus facilitating the opening of their chloride channels and potentiating GABA's inhibitory effect. But now researchers are increasingly finding that the specific effects of each type of benzodiazepine seem to be directly linked to the various types of GABA-A receptors to which it can bind (GABA-A receptors are made up of sub-units designated alpha, beta, and gamma, and the various types of GABA-A receptors represent varying arrangements of these sub-units).

Left: distribution of benzodiazepine receptors in the brain. Right: distribution of D2 dopaminergic receptors

Source: CERMEP, Hôpital Neuro-Cardiologique de Lyon
  Research suggests that different benzodiazepines may have differing affinities for these various types of GABA-A receptors, which may in turn explain why one benzodiazepine has more of an anxiolytic effect while another has more of a sedative effect. Also, some studies show a marked variation in the distribution of these various kinds of benzodiazepine receptors within the brain. For example, the type of benzodiazepine receptor that predominates in the motor and sensory cortexes is not the same one that predominates in the circuits of the amygdala and the other structures of the limbic system.

These studies thus support the idea that the distinctive effects of various benzodiazepines are associated with the different types of receptors and their distribution in the brain.

Some studies seem to show that endocannabinoids—substances that are analogous to the active ingredient in cannabis but that are produced inside the human body—help to extinguish painful memories through their inhibitory effect on the internal circuits of the amygdala.

In one study, for example, mice that had been genetically altered so that they did not express the endocannabinoid receptor had much more trouble in extinguishing a conditioned fear, even though they did not display any other memory problems. (The same result was also obtained when the endocannabinoid receptor was blocked with an antagonist.)

While the mice were being exposed to the stimulus that led to the extinction of the response, the researchers also found high levels of endocannabinoids in the basolateral nucleus of the amygdala, which is known to be involved in the extinction of painful memories. This extinction seems to involve the activation of NMDA receptors by glutamatergic neurons. Endocannabinoid receptors are known to have an inhibitory effect on the GABAergic inhibitory neurons in the basolateral nucleus. Hence one can see how inhibition of these inhibitory neurons by endocannabinoids might lead to activation of the NMDA receptors and thus facilitate extinction of the conditioned fear.

The psychotherapeutic treatment for many anxiety disorders (including phobias) is based on a process of extinction (placing the patient in contact with the feared object in the safe setting of the therapist's office). Hence, if a substance that increased the levels of endocannabinoids at the right places in the patient's brain could be administered during psychotherapy, it might facilitate a cure. (This probably would not be the case if the patient simply smoked a joint, flooding the entire brain with THC.)

Lastly, there are other molecules that also may help to extinguish painful memories. Some of these molecules activate the NMDA receptors in the amygdala, which are also involved in the process of extinction.

Experiment : Never fear, cannabinoids are here Link : Innate cannabis chemical erases fears Link : Some smoke dope to forget Link : Weeding out memory extinction Link : cannabinoid receptor 1
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