2010 - Behavioral Neuroscience of Drug Addiction by Self & Staley

Author:Self & Staley
Language: eng
Format: mobi
Published: 2014-07-28T16:29:55.343000+00:00

Introduction

This chapter will briefly review the literature on differences in the brain chemistry

of individuals with alcohol and drug dependence versus healthy, nondependent

individuals in vivo as measured with positron emission tomography (PET) and

single photon emission computed tomography (SPECT) imaging. Importantly, in

humans we are not able to obtain “baseline” scans on drug dependent individuals

from when they were drug-naı¨ve; thus, data collected in drug abusers are typically

compared to age-matched healthy controls. This means that we do not know

whether the brain changes are pre-existing and represent a vulnerability to addic-

tion, or whether they are a consequence to drug use. PET and SPECT receptor

imaging is typically used to examine the neurochemistry of addiction during early

detoxification and also during longer periods of withdrawal. The length of absti-

nence is an important variable to take into account in imaging studies, because

different receptor systems have been shown to change during the recovery from

drug and alcohol dependence, some in as little as several weeks; thus, length of

Imaging Receptor Changes in Human Drug Abusers

201

abstinence will be noted when it is available. We cannot currently determine in

humans whether differences in receptor or transporter availability are pre-existing

or are a consequence; thus, this alternative conclusion is a caveat in all sections of

this chapter. It is also important to note that many individuals with drug addiction

also drink alcohol and/or smoke cigarettes, making it a complex process to deter-

mine which variable or combination of variables are contributing to the receptor

changes. In the majority of studies, to date, smoking is not systematically con-

trolled; thus, additional research will be required to untangle these relationships.

PET and SPECT may also be used to measure striatal dopamine (DA) transmission,

e.g., drug-induced changes in DA release, and this is covered in another chapter by

Dr. Martinez. We refer to receptor “availability” as opposed to receptor “levels” or

“density” throughout the chapter to note that these studies are measuring receptors

that are available to be bound by the radiotracer. This is because the radiotracer

cannot bind to receptors that are already occupied, perhaps by the drug; e.g.,

cocaine, or an endogenous neurotransmitter such as dopamine. We are currently

able to image a limited number of receptor systems in the brain; thus, the scope of

this review is limited to existing radiotracers that are currently approved for use in

humans.

2

Cocaine

2.1 Cocaine and the Dopamine Transporter

Cocaine acts directly at the DA transporter by blocking the reuptake of dopamine.

Several studies report higher striatal DA transporter availability in acutely abstinent

cocaine-dependent subjects compared to healthy controls using [123I]beta-CIT

SPECT (Jacobsen et al. 2000; Malison et al. 1998). Additionally, higher DA

transporter availability was associated with worse scores on the Hamilton depres-

sion inventory (Malison et al. 1998). However, no difference in striatal DA trans-

porter availability between chronic cocaine abusers (last use of cocaine was 5 Æ 8

days) versus controls, but lower striatal DA transporter availability in detoxified

cocaine abusers (last use 42 Æ 7 days) was reported using [11C]cocaine PET (Wang

et al. 1997a). Differences in these studies are likely due to differences between the

radiotracers [123I]beta-CIT and [11C]cocaine. Specifically, [11C]cocaine is limited

due to its low specific to nonspecific binding ratio and rapid clearance, and thus is

more of a blood flow agent.

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