Sex differences in adult cognitive deficits after adolescent nicotine exposure in rats

Neurotoxicology and Teratology

2015

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Nicotine exposure in adolescent rats has been shown to cause learning impairments that persist into adulthood long after nicotine exposure has ended. This study was designed to assess the extent to which the effects of adolescent nicotine exposure on learning in adulthood can be accounted for by adolescent injection stress experienced concurrently with adolescent nicotine exposure. Female rats received either 0.033 mg/hr nicotine (expressed as the weight of the free base) or bacteriostatic water vehicle by osmotic pump infusion on postnatal days 25-53 (P25-53). Half of the nicotine-exposed rats and half of the vehicle rats also received twice-daily injection stress consisting of intraperitoneal saline injections on P26-53. Together these procedures produced 4 groups: No Nicotine / No Stress, Nicotine / No Stress, No Nicotine / Stress, and Nicotine / Stress. On P65-99, rats were trained to perform a structurally complex 24-element serial pattern of responses in the serial multiple choice (SMC) task. Four general results were obtained in the current study. First, learning for within-chunk elements was not affected by either adolescent nicotine exposure, consistent with past work (Pickens, Rowan, Bevins, & Fountain, 2013), or adolescent injection stress. Thus, there were no effects of adolescent nicotine exposure or injection stress on adult within-chunk learning typically attributed to rule learning in the SMC task. Second, adolescent injection stress alone (i.e., without concurrent nicotine exposure) caused transient but significant facilitation of adult learning restricted to a single element of the 24-element pattern, namely, the “violation element,” that was the only element of the pattern that was inconsistent with pattern structure. Thus, adolescent injection stress alone facilitated violation element acquisition in adulthood. Third, also consistent with past work (Pickens et al., 2013), adolescent nicotine exposure, in this case both with and without adolescent injection stress, caused a learning impairment in adulthood for the violation element in female rats. Thus, adolescent nicotine impaired adult violation element learning typically attributed to multiple-item learning in the SMC task. Fourth, a paradoxical interaction of injection stress and nicotine exposure in acquisition was observed. In the same female rats in which violation-element learning was impaired by adolescent nicotine exposure, adolescent nicotine experienced without adolescent injection stress produced better learning for chunk-boundary elements in adulthood compared to all other conditions. Thus, adolescent nicotine without concurrent injection stress facilitated adult chunk-boundary element learning typically attributed to concurrent stimulus-response discrimination learning and serial-position learning in the SMC task. To the best of our knowledge, the current study is the first to demonstrate facilitation of adult learning caused by adolescent nicotine exposure.

supporting

confidence: 89%

mentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Paradoxical effects of injection stress and nicotine exposure experienced during adolescence on learning in a serial multiple choice (SMC) task in adult female rats

Renaud

Pickens

Neurotoxicology and Teratology

2015

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“…In addition, recent work with a nose poke version of the SMC task has shown that adolescent nicotine exposure causes sex-selective impairments of serial pattern learning in adult rats. Adolescent nicotine causes impairments of acquisition of chunk-boundary elements in male rats and violation elements in female rats, but spares within-chunk element acquisition in both male and female rats (Fountain, Rowan, Kelley, Willey, & Nolley, 2008; Pickens, Rowan, Bevins, & Fountain, 2013). Thus, both behavioral and pharmacological evidence from the SMC task indicate that learning to anticipate chunk-boundary elements, within-chunk elements, and violation elements depends on different underlying cognitive systems and that these dissociable cognitive systems likely depend on dissociable neural systems (Fountain, 2008; Fountain & Rowan, 2000; Fountain et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Central cholinergic involvement in sequential behavior: Impairments of performance by atropine in a serial multiple choice task for rats

Neurobiology of Learning and Memory

Rowan

Wollan

2013

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Two experiments examined whether muscarinic cholinergic systems play a role in rats’ ability to perform well-learned highly-structured serial response patterns, particularly focusing on rats’ performance on pattern elements learned by encoding rules versus by acquisition of stimulus-response (S-R) associations. Rats performed serial patterns of responses in a serial multiple choice task in an 8-lever circular array for hypothalamic brain-stimulation reward. Two experiments examined the effects of atropine, a centrally-acting muscarinic cholinergic receptor antagonist, on rats’ ability to perform pattern elements where responses were controlled by rules versus elements, such as rule-inconsistent “violation elements” and elements following “phrasing cues,” where responses were controlled by associative cues. In Experiment 1, 3-element chunks of both patterns were signaled by pauses that served as phrasing cues before chunk-boundary elements, but one pattern also included a violation element that was inconsistent with pattern structure. Once rats reached a high criterion of performance, the drug challenge was intraperitoneal injection of a single dose of 50 mg/kg atropine sulfate. Atropine impaired performance on elements learned by S-R learning, namely, chunk-boundary elements and the violation element, but had no effect on performance of rule-based within-chunk elements. In Experiment 2, patterns were phrased and unphrased perfect patterns (i.e., without violation elements). To control for peripheral effects of atropine, rats were treated with a series of doses of either centrally-acting atropine or peripherally-acting atropine methyl nitrate (AMN), which does not cross the blood-brain barrier. Once rats reached a high criterion, the drug challenges were on alternate days in the order 50, 25, and 100 mg/kg of either atropine sulfate or AMN. Atropine, but not AMN, impaired performance in the phrased perfect pattern for pattern elements where S-R associations were important for performance, namely, chunk-boundary elements. However, in the structurally more ambiguous unphrased perfect pattern where rats had fewer cues and presumably relied more on S-R associations throughout, atropine impaired performance on all pattern elements. Thus, intact muscarinic cholinergic systems were shown to be necessary for discriminative control previously established by S-R learning, but were not necessary for rule-based serial pattern performance.

Concurrent cognitive processes in rat serial pattern learning: II. Discrimination learning, rule learning, chunk length, and multiple-item memories

Muller

Jrnl Exper Analysis Behavior

2016

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The current experiment examined the factors that determine acquisition for elements of highly structured serial patterns. Three groups of rats were trained on three patterns with parallel rule-based hierarchical structure, but with 3-, 4-, or 5-element chunks, each with a final violation element. Once rats mastered their patterns, probe patterns were introduced to answer several questions. To assess the extent to which the learned response pattern depended on intrachamber location cues for anticipating different element types, Spatial Shift Probes shifted the starting lever of patterns to locations that positioned chunk boundaries where they had never been experienced during training. To assess the extent to which a phrasing cue is necessary for rats to perform a chunk-boundary response, a Cue Removal Probe tested whether rats would produce a chunk-boundary response in the correct serial position if the phrasing cue was omitted. To assess the extent to which cues from multiple trials leading up to the violation element are required to anticipate the violation element, Multiple-Item Memory Probes required rats to make an unexpected response on one of the elements in the last two chunks of the pattern prior to the violation element. The results indicated that rats used multiple concurrent learning and memory processes to master serial patterns, including discrimination learning, rule learning, encoding of chunk length, and multiple-item memories.