Adolescent exposure to fluoxetine impairs serial pattern learning in the serial multiple choice (SMC) task in adult rats

Abstract

The effects of chronic adolescent fluoxetine (FLX, Prozac®) exposure on adult cognition are largely unknown. We used a serial multiple choice (SMC) task to characterize the effects of adolescent FLX exposure on rat serial pattern learning in adulthood. Male rats were exposed to either 1.0, 2.0, or 4.0 mg/kg/day FLX for five consecutive days each week for five weeks during adolescence, followed by a 35-day drug-free period. As adults, the rats were trained in a task that required them to learn a highly structured sequential pattern of responses in an octagonal chamber for water reinforcement. In a transfer phase, the terminal element of the pattern was replaced by a violation element that was inconsistent with previously learned pattern structure. Results indicated that adolescent FLX exposure caused differential learning deficits for different types of elements in the serial pattern. Adolescent exposure to 1.0 or 4.0 mg/kg/day FLX, but not 2.0 mg/kg/day FLX, impaired chunk-boundary element learning, which is known to be mediated by stimulus-response (S-R) learning. All three doses of FLX impaired violation element learning, which is known to be mediated by multiple-cue learning. FLX did not impair within-chunk element learning, which is known to be mediated by rule-learning mechanisms. The results indicate that adolescent FLX exposure produced multiple cognitive impairments that were detectable in adulthood long after drug exposure ended.