Katherine Dyer

•Rats received 1.0, 2.0, or 4.0 mg/kg/day of fluoxetine (FLX) during adolescence.•Rats were trained on a serial multiple choice (SMC) task in adulthood.•Adolescent FLX differentially impaired acquisition of serial pattern element types.•FLX impaired stimulus-response and multiple-cue learning but not rule-learning.•Adolescent exposure to FLX impaired some aspects of adult cognition in rats.
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.

There is a growing body of research on matching- and non-matching-to-sample (MTS, NMTS) relations with rats using olfactory stimuli; however, the specific characteristics of this relational control are unclear. In the current study we examine MTS and NMTS in rats with an automated olfactometer using a successive (go, no-go) procedure. Ten rats were trained to either match- or non-match-to-sample with common scents (apple, cinnamon, etc.) as olfactory stimuli. After matching or non-matching training with four odorants, rats were tested for transfer twice with four new odorants on each test. Most rats trained on MTS showed immediate transfer to new stimuli, and most rats trained on NMTS showed full transfer by the second set of new odors. After meeting criterion on the second transfer test, the contingencies were reversed with four new odor stimuli such that subjects trained on matching were shifted to non-matching and vice versa. Following these reversed contingencies, the effects of the original training persisted for many trials with new odorants. These data extend previous studies on same-different concept formation in rats, showing strong generalization requiring few exemplars. The critical role of olfactory stimuli is discussed.