May 30, 2001. Copyright 2001. Graphic News. All rights reserved. Single recreational cocaine dose may prime brain for addiction LONDON, May 30, Graphic News: A single exposure to cocaine triggers a week-long surge of activity in a brain region central to the development of addiction, according to new research on mice published this week in the science journal Nature. Scientists say this stimulus may prime the brain for addiction. The research shows that the first exposure to cocaine -- or the highly potent, smokable form of the drug, ÒcrackÓ -- hijacks a neural Òreward pathwayÓ in a part of the brain that developed in our mammalian ancestors more than 100 million years ago. These primitive, Òhard-wiredÓ circuits in the brainstem and midbrain are responsible for our most basic emotions and behaviours, including feeding, fighting and sex. Cocaine works by stimulating neurons (nerve cells) which extend from an area known as the tegmentum of the midbrain, found atop the brainstem, to the nucleus accumbens reward centre. Neural switches in this pathway are locked in the ÒonÓ position making the brain acutely responsive to subsequent drug exposure for up to ten days, accelerating the memory formation that underlies addiction, according to the scientists. Reward pathways, like all neural circuits, contain synapses -- small gaps between nerve cells which are bridged by chemical neurotransmitters such as dopamine. A neuron releases minute quantities of dopamine which stimulate receptors on an adjacent nerve cell, enabling electrical signals to be transmitted around the brain. At the same time, the first neuron undergoes a recovery period: recharging by taking up dopamine from the receptors and synaptic gap until, a microsecond later, it is ready to fire again. Cocaine blocks the takeup of dopamine by the first neuron, leading to excessive stimulation of the reward pathway. The research, led by a team at the University of California, San FranciscoÕs Ernest Gallo Clinic and Research Center, provides the first direct evidence that a single cocaine exposure -- comparable in humans to a recreational dose -- causes dramatic changes in the brain, accelerating learning and memory formation which are known to play a key role in the experience of a drug high and subsequent drug craving. ÒThe study shows that the capacity for strengthening connections between nerve cells -- the basis for learning and memory -- can be usurped by drugs of abuse,Ó said Antonello Bonci, MD, senior author of the paper. ÒThe single exposure appears to hijack the brainÕs normal molecular mechanisms of memory formation for around a week,Ó he said. Previous research has linked learning and memory, involving activation of the dopamine neurons in the midbrain tegmental area, to the development of addiction. The new study used electrophysiological tests of brain tissue from cocaine-treated mice to show this activity was induced by a single cocaine exposure. ÒDemonstrating that this key process actually occurs following any kind of learning has been difficult,Ó said Mark Ungless, PhD, a post-doctoral scientist at UCSF and lead author on the paper. ÒWhen you learn something, you might expect to see a change in very few synaptic connections -- the junctions between communicating neurons. WhatÕs so amazing is that nearly all dopamine neurons are affected by this single cocaine exposure. This kind of response is extremely rare, and would have a profound effect throughout the brain, particularly other areas involved in addiction.Ó Ungless and Bonci hope their research can lead to new approaches to treatment of drug addiction. ÒThe question,Ó Bonci said, Òis how to develop drugs that interfere with these cocaine-induced changes but not with normal memory formation. This is something we plan to explore.Ó /ENDS Source: Nature