Neuroscience Of Addictions |

Neuroscience of Addictions

Cocaine and Methamphetamine - Neuroscience of Addictions
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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).
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.
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),
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: 27162738.
Sekine, Yoshimoto, et al. (2001). "Methamphetamine-related psychiatric symptoms and reduced
brain dopamine transporters studied with PET." American Journal of Psychiatry 158.8:
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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