Rats learned serial patterns composed of either "run" chunks (e.g., 123 234 ...) or "trill" chunks (e.g., 121 232 ...). For each type of pattern, 1 group of rats encountered an element at the end of the pattern that violated the run or trill structure. In both run and trill patterns, violations were unusually difficult for rats to learn, whereas corresponding elements in "perfect" patterns that did not violate pattern structure were easy. Additionally, rats' errors on violation elements conformed to the structure of the patterns in which they were embedded. Thus, rats were sensitive to the run or trill organization of their patterns and mastered the rules governing the pattern before learning "exceptions to the rule."

In 3 experiments, rats and humans learned serial patterns composed of 24, 30, or 36 items. Patterns had a 2-, 3-, or 4-level hierarchical rule structure. In Experiments 1 and 2, patterns had either perfect hierarchical structure or 2 modified chunks that violated hierarchical structure, thus producing linear structure (i.e., nonhierarchical structure). For both rats and humans, pattern structure predicted pattern learning difficulty and also the nature and relative frequency of errors. Both treated chunks that were inconsistent with hierarchical structure as violation chunks, that is, they made errors that reflected their "tendency to regularize the perception of an irregular pattern" (F. Restle & B. L. Burnside, 1972). The results support the view that rats can abstract and encode a representation of multilevel hierarchical structure in serial patterns in much the same way as humans do in analogous tasks.

In the present study investigating the effects of adolescent nicotine exposure on adult serial pattern learning, adolescent rats received daily i.p. injections of either 1.0 mg/kg nicotine or saline for 5 days per week for 5 weeks beginning on postnatal day 25 (P25), then were allowed 35 days drug free. Rats then began training on P95 as adults on a 24-element serial pattern composed of eight 3-element chunks. Adolescent exposure to 1.0 mg/kg nicotine produced persistent retardation of learning for the first element of each 3-element chunk of the pattern, that is, for chunk boundary elements, and transient retardation of learning for elements 2 and 3 of each chunk of the pattern, that is, for the within-chunk elements. Deficits at chunk boundaries were interpreted as deficits of phrasing cue discrimination learning whereas deficits for learning responses for elements within-chunks (elements 2 and 3 of chunks) were interpreted as deficits of rule learning. These results indicate that the effects of adolescent nicotine exposure on adult learning and cognitive capacity deserve further scrutiny.

Cigarette smoking by adolescents is a strong predictor of future drug use, abuse, and dependence. While this "gateway drug effect" is assumed to be related to psychosocial factors, data from our laboratory suggests that adolescent nicotine use may permanently disrupt reward systems through changes in dopamine receptor function. Behavioral pharmacological methods known to be indirectly (motor activity) and directly (conditioned-place-preference) related to drug reinforcement were used to examine changes in cocaine sensitivity. Testing was performed on adult mice that were exposed to nicotine (0.3, 1.0, and 3.0 mg/kg, SC, M-F, b.i.d.) or saline during adolescence (postnatal days 25-57). Prior to testing, subjects had a 28 day drug-free, time-off period. After acclimation to the testing apparatus, the locomotor effects (30 min, 30 cm traveled) of cocaine (5, 10, and 20 mg/kg, IP) were measured daily; cocaine tests were preceded and followed by saline control tests. Following the acute dose-response curve, mice received saline followed by 5 days of 20.0 mg/kg cocaine. Thereafter, mice underwent condition-place-preference testing. A pre-test was performed to determine compartment preference (i.e., no injection, 20 min test). Cocaine (10 mg/kg, IP) was paired with the subjects non-preferred side and saline with the other. Conditioning sessions were conducted for 8 days with the order of drug/saline injections counter-balanced across subjects. A drug-free, post-test occurred on the day following the final conditioning session. A dose-dependent relationship between adolescent nicotine exposure and cocaine reward was noted in the adult mice across both test conditions. Subjects exposed to nicotine showed an increased response to cocaine's motor activating effects and a decreased response to cocaine's rewarding effects. A follow-up study was undertaken to evaluate dopamine D1, D2, and D3 receptor function in adult mice exposed to the highest dose of nicotine from the first study. While both interesting and revealing, the results of motor activity tests with dopamine agonist only approached significance. Further research will be required to more fully examine the mechanism of action for the observed changes in cocaine reward. In summary, this is the first study to demonstrate a dose-response relationship between adolescent nicotine exposure and changes in cocaine reward and sensitivity during adulthood.

This study was designed to determine whether deficits in adult serial pattern learning caused by adolescent nicotine exposure persist as impairments in asymptotic performance, whether adolescent nicotine exposure differentially retards learning about pattern elements that are inconsistent with “perfect” pattern structure, and whether there are sex differences in rats’ response to adolescent nicotine exposure as assessed by a serial multiple choice task. The current study replicated the results of our initial report (Fountain, Rowan, Kelley, Willey, & Nolley, 2008) using this task by showing that adolescent nicotine exposure (1.0 mg/kg/day nicotine for 35 days) produced a specific cognitive impairment in male rats that persisted into adulthood at least a month after adolescent nicotine exposure ended. In addition, sex differences were observed even in controls, with additional evidence that adolescent nicotine exposure significantly impaired learning relative to same-sex controls for chunk boundary elements in males and for violation elements in females. All nicotine-induced impairments were overcome by additional training so that groups did not differ at asymptote. An examination of the types of errors rats made indicated that adolescent nicotine exposure slowed learning without affecting rats’ cognitive strategy in the task. This data pattern suggests that exposure to nicotine in adolescence may have impaired different aspects of adult stimulus-response discrimination learning processes in males and females, but left abstract rule learning processes relatively spared in both sexes. These effects converge with other findings in the field and reinforce the concern that adolescent nicotine exposure poses an important threat to cognitive capacity in adulthood.