Friday, March 15, 2013

Stimulants, Opiates and the Human Brain

Chemical stimulants such as cocaine and opiates such as morphine profoundly influence behavior through their interaction with and alteration of brain chemistry.  Members of the opiate family of compounds are known to markedly reduce the experience of pain.  Of particular interest in this regard is the neurotrophic factor, BDNF – a direct product of brain chemistry.  BDNF plays a very important role in maintaining so-called “neural plasticity.”  This plasticity represents an intrinsic ability of the human brain to alter neuronal pathways and synapses – the junctions between nerve cells that allow the passage of electrical signals through the nervous system – in response to changes in behavior and the environment especially in regard to bodily injury.  This is a highly adaptive function of the brain that is often seen in the victims of stroke – allowing individuals to compensate for brain damage.

BDNF has been shown to play a key role in the kind of neural and behavioral plasticity that is induced by the use of cocaine and other stimulants.  Furthermore, it has been demonstrated that the mode of action of BDNF in this regard is intimately connected with the mesolimbic dopamine (DA) system that represents a key reward circuit in the brain.  Dopamine is one of major neurotransmitters in the brain that is involved in many diverse brain functions.  It is the irreversible loss of dopamine-producing cells that results in the symptoms associated with Parkinson’s disease.  The net result of the interaction of BDNF with DA system is the promotion of further actions of stimulant drugs.

Dr. Ja Wook Koo and his colleagues at the Fishberg Department of Neuroscience and Friedman Brain Institute at the Mount Sinai School of Medicine in New York have implicated BDNF in the mode of action of the opiate drug, morphine and have helped elucidate the mechanism through which it works.  In contrast to stimulants, opiates exert their effect on the brain through the promotion of DA signaling by the inhibition of ϒ-aminobutyric acid (GABA) – an important neurotransmitter in the brain that plays a role in regulating neuronal excitability through an inhibitory pathway.  The investigators have clearly shown that BDNF is, in fact, a negative modulator of morphine action.

This is an important finding in that is helps elucidate the mechanisms involved  with  brain-associated adaptations within the reward circuitry that occur with the use of morphine – a drug that is widely used to treat severe chronic pain especially at the end of life. 

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