Premium
Improved cognitive flexibility in serotonin transporter knockout rats is unchanged following chronic cocaine self‐administration
Author(s) -
kes Lourens J. P.,
Maes Joseph H. R.,
Homberg Judith R.
Publication year - 2013
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/j.1369-1600.2011.00351.x
Subject(s) - cognitive flexibility , serotonin transporter , self administration , psychology , cognition , serotonin , flexibility (engineering) , pharmacology , endocrinology , medicine , neuroscience , receptor , statistics , mathematics
Cocaine dependence is associated with orbitofrontal cortex (OFC)‐dependent cognitive inflexibility in both humans and laboratory animals. A critical question is whether cocaine self‐administration affects pre‐existing individual differences in cognitive flexibility. Serotonin transporter knockout (5‐HTT −/− ) mice show improved cognitive flexibility in a visual reversal learning task, whereas 5‐HTT −/− rats self‐administer increased amounts of cocaine. Here we assessed: (1) whether 5‐HTT −/− rats also show improved cognitive flexibility (next to mice); and (2) whether this is affected by cocaine self‐administration, which is increased in these animals. Results confirmed that naïve 5‐HTT −/− rats ( n = 8) exhibit improved cognitive flexibility, as measured in a sucrose reinforced reversal learning task. A separate group of rats was subsequently trained to intravenously self‐administer cocaine (0.5 mg/kg/infusion), and we observed that the 5‐HTT −/− rats ( n = 10) self‐administered twice as much cocaine [632.7 mg/kg (±26.3)] compared with 5‐HTT +/+ rats ( n = 6) [352.3 mg/kg (±62.0)] over 50 1‐hour sessions. Five weeks into withdrawal the cocaine‐exposed animals were tested in the sucrose‐reinforced reversal learning paradigm. Interestingly, like the naïve 5‐HTT −/− rats, the cocaine exposed 5‐HTT −/− rats displayed improved cognitive flexibility. In conclusion, we show that improved reversal learning in 5‐HTT −/− rats reflects a pre‐existing trait that is preserved during cocaine‐withdrawal. As 5‐HTT −/− rodents model the low activity s‐allele of the human serotonin transporter‐linked polymorphic region, these findings may have heuristic value in the treatment of s‐allele cocaine addicts.