Neuroscience Of Addictions

Running head: COCAINE AND METHAMPHETAMINE - NEUROSCIENCE OF ADDICTIONS 1

Cocaine and Methamphetamine - Neuroscience of Addictions

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COCAINE AND METHAMPHETAMINE - NEUROSCIENCE OF ADDICTIONS 2

Cocaine and Methamphetamine - Neuroscience of Addictions

Mechanisms by which Methamphetamine Affect Dopamine Transporters

Several studies have shown a reduction in varied dopamine transporters in the striatum of

methamphetamine abusers using PET (positron emission tomography) scans (Sekine et al., 2001:

Volkow et al., 2001). Volkow et al. found an average difference of about 21% (21.1%) in the

putamen to 28% (27.8%) in the caudate (2001).

Another study reveals that upon intake of methamphetamine, dopamine uptake increases

only to a satiation point despite continued dopamine transporter binding. However, this observed

Dopamine (³H) uptake inhibition is reversed after 24 hours (Kokoshkaa et al., 1998). Another

corroborating study conducted on rats suggested that this inhibition mechanism might be related

to species-specific oxygen levels in the blood (Fleckenstein, 1997).

Also, methamphetamine users who successfully abstained from relapse can recover.

Subjects of a study were tested for dopamine transporters at 6 months and between 12-17 months

of prolonged abstinence. Dopamine transporters increased marginally showing that recovery is

indeed possible. However, the study cautioned that the remaining dopamine transporters could

have adapted to allow for higher uptake since the recovery did not match normal levels (Volkow

et al., 2001).

COCAINE AND METHAMPHETAMINE - NEUROSCIENCE OF ADDICTIONS 3

Contrasting the Effects of Methamphetamines and Cocaine on Dopamine Transporters

Cocaine is also another powerful psychoactive agent that acts upon dopamine

transporters. However, unlike methamphetamine, it increases dopamine uptake significantly and

for longer (Daws et al., 2002). This is why cocaine has a longer high than methamphetamines.

Daws et al. showed that cocaine not only boosts dopamine uptake levels but disrupts equilibrium

by mass activation of dopamine transporters except for one (2002).

Cocaine is also reliant on dopamine transporters as shown in a study where mice without

them were indifferent to its effects (Giros et. al., 1996).

In contradictory fashion, cocaine only seems to increase dopamine transporters from

initial use blocking specific dopamine transporters thereafter like methamphetamine. This

reduction means there are less active binding receptors to supply the dopamine uptake resulting

in a reinforcing loop of increasing cravings. Fewer dopamine transporters increase the uptake

load. Anecdotal evidence (Ritz, Cones and Kuhar, 1996: Volkow et al., 2000) for this existed in

the past without definitive proof of the blocked dopamine transporters.

A recent study identified dopamine transporter 5-HT abbreviated as SERT as the site for

cocaine’s blockade that results in reinforcement (Simler et al., 2017). Interesting enough, the

dopamine transporter 5-HT 6 which is a variation of SERT is blocked by amphetamines too.

These variations of dopamine transporter blockades could be the causal link for reinforced

addiction in both cocaine and methamphetamine.

COCAINE AND METHAMPHETAMINE - NEUROSCIENCE OF ADDICTIONS 4

References

Daws, L. C., Callaghan, P. D., Morón, J. A., Kahlig, K. M., Shippenberg, T. S., Javitch, J. A., &

Galli, A. (2002). Cocaine increases dopamine uptake and cell surface expression of

dopamine transporters. Biochemical and biophysical research communications, 290(5),

1545-1550.

Giros, B., Jaber, M., Jones, S. R., Wightman, R. M., & Caron, M. G. (1996). Hyperlocomotion

and indifference to cocaine and amphetamine in mice lacking the dopamine transporter.

Nature, 379(6566), 606.

Fleckenstein, A. E., Metzger, R. R., Wilkins, D. G., Gibb, J. W., & Hanson, G. R. (1997). Rapid

and reversible effects of methamphetamine on dopamine transporters. Journal of

Pharmacology and Experimental Therapeutics, 282(2), 834-838.

Kokoshka, J. M., Vaughan, R. A., Hanson, G. R., & Fleckenstein, A. E. (1998). Nature of

methamphetamine-induced rapid and reversible changes in dopamine transporters.

European journal of pharmacology, 361(2), 269-275.

Ritz, M. C., Cone, E. J., & Kuhar, M. J. (1990). Cocaine inhibition of transporter binding at

dopamine, norepinephrine and serotonin transporters: a structure-activity study. Life

sciences, 46(9), 635-645.

Simmler, L. D., Anacker, A. M. J., Levin, M. H., Vaswani, N. M., Nackenoff, A. G., Anastasio, N.

C., Stutz, S. J., Cunningham, K. A., Wang, J., Zhang, B., Henry, L. K., Stewart, A.,

Veenstra-VanderWeele, J., and Blakely, R. D. (2017). Blockade of the 5-HT transporter

contributes to the behavioural, neuronal and molecular effects of cocaine. British Journal

of Pharmacology, 174: 2716–2738.

COCAINE AND METHAMPHETAMINE - NEUROSCIENCE OF ADDICTIONS 5

Sekine, Yoshimoto, et al. (2001). "Methamphetamine-related psychiatric symptoms and reduced

brain dopamine transporters studied with PET." American Journal of Psychiatry 158.8:

1206-1214.

Volkow, N. D., Chang, L., Wang, G. J., Fowler, J. S., Leonido-Yee, M., Franceschi, D., & Logan,

J. (2001). Association of dopamine transporter reduction with psychomotor impairment in

methamphetamine abusers. American Journal of Psychiatry, 158(3), 377-382.

Volkow, N. D., Wang, G. J., Fischman, M. W., Foltin, R., Fowler, J. S., Franceschi, D., & Ding,

Y. S. (2000). Effects of route of administration on cocaine induced dopamine transporter

blockade in the human brain. Life sciences, 67(12), 1507-1515.

Volkow, N. D., Chang, L., Wang, G. J., Fowler, J. S., Franceschi, D., Sedler, M., & Logan, J.

(2001). Loss of dopamine transporters in methamphetamine abusers recovers with

protracted abstinence. Journal of Neuroscience, 21(23), 9414-9418.

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