TY - JOUR
T1 - Ultrahigh-resolution MRI reveals structural brain differences in serotonin transporter knockout rats after sucrose and cocaine self-administration
AU - Karel, Peter
AU - van der Toorn, Annette
AU - Vanderschuren, Louk
AU - Guo, Chao
AU - Sadighi Alvandi, Mina
AU - Reneman, Liesbeth
AU - Dijkhuizen, Rick
AU - Verheij, Michel M. M.
AU - Homberg, Judith R.
N1 - Funding Information: The work described in this paper was funded by The Netherlands Organization for Health Research and Development (ZonMw, project number 91211002 awarded to J.H.). ZonMw had no further role in the design of the study; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Publisher Copyright: © 2019 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Excessive use of cocaine is known to induce changes in brain white and gray matter. It is unknown whether the extent of these changes is related to individual differences in vulnerability to cocaine addiction. One factor increasing vulnerability involves reduced expression of the serotonin transporter (5-HTT). Human studies have shown that inherited 5-HTT downregulation is associated with structural changes in the brain. These genotype-related structural changes may contribute to risk for cocaine addiction. Here, we tested this idea by using ultrahigh-resolution structural magnetic resonance imaging (MRI) on postmortem tissue of 5-HTT −/− and wild-type (5-HTT +/+ ) rats with a history of long access to cocaine or sucrose (control) self-administration. We found that 5-HTT −/− rats, compared with wild-type control animals, self-administered more cocaine, but not sucrose, under long-access conditions. Ultrahigh-resolution structural MRI subsequently revealed that, independent of sucrose or cocaine self-administration, 5-HTT −/− rats had a smaller amygdala. Moreover, we found an interaction between genotype and type of reward for dorsal raphe nucleus volume. The data point to an important but differential role of the amygdala and dorsal raphe nucleus in 5-HTT genotype–dependent vulnerability to cocaine addiction.
AB - Excessive use of cocaine is known to induce changes in brain white and gray matter. It is unknown whether the extent of these changes is related to individual differences in vulnerability to cocaine addiction. One factor increasing vulnerability involves reduced expression of the serotonin transporter (5-HTT). Human studies have shown that inherited 5-HTT downregulation is associated with structural changes in the brain. These genotype-related structural changes may contribute to risk for cocaine addiction. Here, we tested this idea by using ultrahigh-resolution structural magnetic resonance imaging (MRI) on postmortem tissue of 5-HTT −/− and wild-type (5-HTT +/+ ) rats with a history of long access to cocaine or sucrose (control) self-administration. We found that 5-HTT −/− rats, compared with wild-type control animals, self-administered more cocaine, but not sucrose, under long-access conditions. Ultrahigh-resolution structural MRI subsequently revealed that, independent of sucrose or cocaine self-administration, 5-HTT −/− rats had a smaller amygdala. Moreover, we found an interaction between genotype and type of reward for dorsal raphe nucleus volume. The data point to an important but differential role of the amygdala and dorsal raphe nucleus in 5-HTT genotype–dependent vulnerability to cocaine addiction.
KW - cocaine self-administration
KW - serotonin transporter knockout rat
KW - structural MRI
UR - http://www.scopus.com/inward/record.url?scp=85061443405&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/adb.12722
DO - https://doi.org/10.1111/adb.12722
M3 - Article
C2 - 30748070
SN - 1355-6215
VL - 25
SP - e12722
JO - Addiction Biology
JF - Addiction Biology
IS - 1
M1 - e12722
ER -