Alternate orders of exposure to nicotine and cocaine were examined. The authors found that pretreatment with nicotine greatly alters the response to cocaine in terms of addiction-related behavior and synaptic plasticity (changes in synaptic strength) in the striatum, a brain region critical for addiction-related rewards. On a molecular level, nicotine also primes the response to cocaine by inhibiting the activity of an enzyme―histone deacetylase―in the striatum. This inhibition enhances cocaine’s ability to activate a gene called FosB gene, which promotes addiction. The relationship between nicotine and cocaine was found to be unidirectional: nicotine dramatically enhances the response to cocaine"
Health News - Nicotine “Primes” the Brain for Cocaine Use: The Molecular Basis of the Gateway Sequence of Drug Use for Nicotine and Cocaine: "Cigarettes and alcohol serve as gateway drugs, which people use before progressing to the use of marijuana and then to cocaine and other illicit substances; this progression is called the “gateway sequence” of drug use. An article in Science Translational Medicine by study author Denise Kandel, PhD, of the Mailman School of Public Health; and Amir Levine, MD; Eric Kandel, MD; and colleagues at Columbia University Medical Center provides the first molecular explanation for the gateway sequence.
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