Free The Addicted Brain by Michael Kuhar Page A

norepinephrine, two additional neurotransmitters. Moreover, cocaine produces a local analgesia by blocking sodium channels in nerves, and it has other actions, too. So, which is the site that makes cocaine an abused drug? A team at the National Institute on Drug Abuse, lead by Drs. Mike Kuhar and Mary Ritz, compared the capability of cocaine and several cocaine analogs to inhibit the uptake of neurotransmitters with the capability of these chemicals to be self-administered (SA) by animals. The drugs that were potent at the DAT were the ones potent in drug SA, and the drugs weak at DAT were the ones weak in SA. This correlation was strong and statistically valid. There was other existing evidence for this at the time, but this binding experiment solidly confirmed the idea. The reference is Ritz M et. al. “Cocaine Receptors on Dopamine Transporters Are Related to the Self-Administration of Cocaine.”
Science,
237: 1219–1223, (1987).
    4 An example of a study with animals showing that compounds with a faster onset of action were better reinforcers is Kimmel H et al.
Pharmacol Biochem Behav,
86:45–54, 2007. An example of a study with human subjects showing that the rate of entry of cocaine into the brain determines its reinforcing (addicting) effects, as described in the text is Volkow N.D. et al.
Life Sciences
, 67:1507–1515, 2000.
    5 Ibid.
    6 This idea derives from studies of the sensory systems in our bodies. Many highly technical experiments on vision and touch show that individual neurons in the periphery and brain respond to
changes
, either increases or decreases, in stimuli. For example, this can be seen in the responses of ganglion cells in the retina, in cortical neurons responding to mechanoreceptors, and in rapidly adapting mechanoreceptors in skin. Details of these studies can be found in a textbook such as Kandel et al.,
Principles of Neural Science
, Third edition (Appleton and Lange, 1991). While the rush derived from drugs has not yet been subjected to such careful scrutiny, it seems reasonable to propose that a drug-induced high or rush is due to
changes
in the basic sensations.

7. The Brain Is Changed—For a Long Time!
    “Before I started drugs, I did great. I never had a hang-up like this. I can’t seem to get over wanting drugs, no matter how hard I try. I stay away from the stuff for weeks, but it doesn’t seem to make a difference. I keep going back.”
    Why is drug addiction so long lasting? Just because drugs exert
powerful
actions in the brain doesn’t mean that their effects should last a
long time
. But they do! How do we study this?
Looking at the Drug User’s Brain
    Brain imaging is a remarkably powerful tool that enables us to peer inside the skull and brain (see Figure 7-1 ), and measure various quantities associated with neurotransmission and drugs. There are various types of imaging that tell us different things. Positron Emission Tomography (PET) scanning 1 can measure both the levels of some proteins (such as receptors) and their levels of activity as well as glucose metabolism in certain regions (see “ PET Scanning ”).
    Figure 7-1. Understanding brain images. Imaging machines look inside the head and brain and display slices of the brain. The schematic on the left shows three different ways or planes that the human brain can be sliced in. Sometimes structures of interest are better seen in one plane or another. Brain imaging instruments look at slices of the brain and reconstruct them so that the details of structure (or function) can be seen, as on the right. The images on the right were obtained using magnetic resonance imaging (MRI). Although the schematic images on the left show only the brain, the actual brain images shown on the right include the skull, eyes, nose, and other tissues, which are more realistic. The PET images shown in Figures 7-2 and 7-3 are horizontal sections that reveal the distribution of radioactivity in slices of the brain. (Adapted from