Drug
and
Alcohol
Dependence
124 (2012) 149–
153
Contents
lists
available
at
SciVerse
ScienceDirect
Drug
and
Alcohol
Dependence
jo
u
rn
al
hom
epage:
www.elsevier.com/locate/drugalcdep
Escalation
of
methamphetamine
self-administration
in
adolescent
and
adult
rats
Justin
J.
Anker
∗
, Thomas
R.
Baron, Natalie
E.
Zlebnik, Marilyn
E.
Carroll
University
of
Minnesota,
Department
of
Psychiatry,
MMC
392,
Minneapolis,
MN
55455,
USA
a
r
t
i
c
l
e
i
n
f
o
Article
history:
Received
12
August
2011
Received
in
revised
form
16
December
2011
Accepted
6
January
2012
Available online 2 February 2012
Keywords:
METH
Adolescence
Escalation
Bingeing
Rat
a
b
s
t
r
a
c
t
Background:
Methamphetamine
(METH)
use
has
increased
substantially
in
the
last
10
years
and
poses
a
serious
health
concern,
especially
for
young
populations.
Drug
abuse
primarily
begins
during
adoles-
cence,
when
uninhibited
and
excessive
and
drug
intake
is
a
common
occurrence;
thus,
understanding
the
developmental
patterns
of
addiction
during
this
critical
period
is
an
essential
step
in
its
prevention.
In
the
present
study,
the
effect
of
age
on
the
vulnerability
to
METH
abuse
was
examined
using
a
rat
model
of
bingeing
(i.e.,
escalation).
Methods:
Adolescent
and
adult
rats
were
compared
during
short
(ShA,
2-h)
and
long-access
(LgA,
6-h)
to
METH
self-administration.
On
postnatal
(PN)
days
23
(adolescents)
and
90
(adults),
rats
were
implanted
with
i.v.
catheters
and
trained
to
lever
press
for
infusions
of
METH
(0.05
mg/kg)
during
2-h
sessions.
Once
the
rats
reached
a
steady
rate
of
METH
self-administration,
they
were
divided
into
ShA
or
LgA
groups
and
allowed
to
self-administer
METH
for
15
additional
days.
Results:
Results
indicated
that
adolescent
rats
earned
significantly
more
infusions
than
adults
under
the
LgA
condition,
but
the
age
groups
did
not
differ
during
ShA.
Adolescents,
but
not
adults,
also
significantly
increased
(i.e.,
escalated)
METH
self-administration
across
the
15
days
of
testing
under
the
LgA
condition.
Further
analysis
indicated
excessive
responding
during
infusions
in
the
LgA
METH-exposed
adolescents
compared
to
the
other
groups,
suggesting
elevated
impulsivity
or
motivation
for
drug.
Conclusion:
These
results
demonstrate
that
adolescents
are
more
vulnerable
to
the
escalation
of
METH
than
adults
during
LgA.
© 2012 Elsevier Ireland Ltd. All rights reserved.
1.
Introduction
Methamphetamine
(METH)
use
is
a
widespread
problem
(Rawson
et
al.,
2007).
The
United
Nations
Office
of
Drug
and
Crime
estimates
that
between
13.7
and
52.9
million
people
used
an
amphetamine-like
substance
at
least
once
in
2010
(nearly
half
the
North
American
users
consumed
METH),
figures
similar
to
or
exceeding
cocaine
or
heroin
on
a
global
scale.
The
growing
pop-
ularity
of
METH
is
attributed
to
its
potency
and
price.
The
street
cost
of
METH
has
continually
decreased
over
the
past
decade
while
the
drug’s
purity
and
availability
have
increased,
thus
making
first
time
use
more
accessible
and
more
addictive
(World
Drug
Report,
2010).
Adolescents
may
be
particularly
vulnerable
to
METH
abuse
given
the
drug’s
growing
popularity,
availability,
potency,
and
low
price,
and
data
from
U.S.
treatment
programs
indicate
that
adoles-
cents
comprise
more
than
20%
of
those
admitted
for
METH
abuse
or
dependence
(Rawson
et
al.,
2007;
Gonzales
et
al.,
2008).
Drug
use
generally
starts
and
progresses
more
rapidly
during
adolescence.
For
example,
the
time
from
the
initial
use
to
the
onset
of
dependence
for
most
drugs
of
abuse
is
shorter
in
adolescents
∗
Corresponding
author.
Tel.:
+1
612
626
6301;
fax:
+1
612
624
8935.
E-mail
address:
anke0022@umn.edu
(J.J.
Anker).
compared
to
adults
(Clark
et
al.,
1998),
and
once
dependence
develops,
adolescents
are
more
likely
to
engage
in
harmful
and
potentially
lethal
drug
binges
(Baumeister
and
Tossmann,
2005;
Estroff
et
al.,
1989;
McCambridge
and
Strang,
2005).
Even
if
abstinence
does
occur,
adolescents
are
more
resistant
to
treatment
interventions
and
are
at
an
increased
risk
for
relapse
compared
to
adults
(Brown
and
D’Amico,
2001;
Catalano
et
al.,
1990;
Chung
et
al.,
2006;
Dennis
et
al.,
2004;
Perepletchikova
et
al.,
2008;
Winters
and
Lee,
2008).
These
drug
abuse
patterns
are
enduring,
as
epi-
demiological
evidence
indicates
that
adolescence
marks
a
period
when
individuals
are
most
susceptible
to
developing
lifelong
drug
addiction
(Schramm-Sapyta
et
al.,
2009;
Spear,
2004,
2010;
Spear
and
Varlinskaya,
2005,
2010;
Doremus-Fitzwater
et
al.,
2010).
Animal
models
have
helped
characterize
underlying
factors
that
influence
drug
abuse
vulnerability
in
adolescents.
This
work
has
indicated
that
adolescents
(vs.
adults)
are
less
sensitive
to
the
aver-
sive
aspects
of
drugs
of
abuse
such
as
negative
withdrawal-related
effects
that
may
otherwise
limit
drug
intake
(Doremus
et
al.,
2003;
Infurna
and
Spear,
1979;
Kota
et
al.,
2007;
O’Dell
et
al.,
2007a,b;
Schramm-Sapyta
et
al.,
2006;
Spear,
2010;
Spear
and
Varlinskaya,
2005;
Varlinskaya
and
Spear,
2004a,b;
Doremus-Fitzwater
et
al.,
2010).
Furthermore,
several
studies
have
indicated
that
adolescents
consume
greater
amounts
of
cocaine
per
kg
of
body
weight
(Anker
and
Carroll,
2010;
Anker
et
al.,
2011;
Perry
et
al.,
2007),
are
more
0376-8716/$
–
see
front
matter ©
2012 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.drugalcdep.2012.01.004