Indiana University-Purdue University Indianapolis (IUPUI)Adolescent alcohol abuse is a global problem that initiates lifelong addiction.
Alcohol use during adolescence is associated with subsequent Meth dependence in
humans. Specifically, female adolescents are particularly vulnerable to serial alcohol and
Meth use. However, it is unknown if prior voluntary alcohol drinking impacts subsequent
Meth-taking in female adolescent rats. Both alcohol and Meth increase the prostaglandin
synthesis enzyme cyclooxygenase-2 (COX-2) in the brain but the effect of serial exposure
to alcohol and Meth on COX-2 has not been determined. The first study uses a novel
method of serial voluntary alcohol drinking and Meth self-administration in female
adolescent rats to model human patterns of co-abuse. Prior alcohol drinking did not affect
subsequent Meth self-administration, but it reduced the cue-primed reinstatement of Methseeking
after abstinence from Meth. Rats with a history of adolescent alcohol drinking also
had increased COX-2 in the dorsal striatum, regardless of subsequent Meth selfadministration.
These findings demonstrate that a history of adolescent alcohol drinking
does not alter Meth self-administration but persistently reduces cue-primed Meth seeking
and increases COX-2 after prolonged abstinence from alcohol. To further examine the role
of COX-2 in alcohol drinking, the second study found that adolescent alcohol drinking not
only increased COX-2 after four weeks of alcohol abstinence, but also increased
endothelin-1 (ET-1) and prostaglandin E2 (PGE2) in the dorsal striatum. Furthermore,
adolescent alcohol drinking increased alcohol drinking after abstinence, and this increase
was attenuated by treatment with the COX-2 inhibitor nimesulide during abstinence.
Antagonism of the interaction between PGE2 and its receptor 1 (EP1) also attenuated the
increase in relapse drinking and restored alcohol drinking to the rate of alcohol naïve rats.
Overall, these experiments identified a prostaglandin-mediated mechanism that is a
putative target for the treatment of alcohol relapse following abstinence in individuals with
a history of adolescent alcohol abuse
