title: Biological sex influences learning strategy preference and muscarinic receptor binding in specific brain regions of prepubertal rats.
abstract: According to the theory of multiple memory systems, specific brain regions interact to determine how the locations of goals are learned when rodents navigate a spatial environment. A number of factors influence the type of strategy used by rodents to remember the location of a given goal in space, including the biological sex of the learner. We recently found that prior to puberty male rats preferred a striatum-dependent stimulus-response strategy over a hippocampus-dependent place strategy when solving a dual-solution task, while age-matched females showed no strategy preference. Because the cholinergic system has been implicated in learning strategy and is known to be sexually dimorphic prior to puberty, we explored the relationship between learning strategy and muscarinic receptor binding in specific brain regions of prepubertal males and female rats. We confirmed our previous finding that at 28 days of age a significantly higher proportion of prepubertal males preferred a stimulus-response learning strategy than a place strategy to solve a dual-solution visible platform water maze task. Equal proportions of prepubertal females preferred stimulus-response or place strategies. Profiles of muscarinic receptor binding as assessed by autoradiography varied according to strategy preference. Regardless of biological sex, prepubertal rats that preferred stimulus-response strategy exhibited lower ratios of muscarinic receptor binding in the hippocampus relative to the dorsolateral striatum compared to rats that preferred place strategy. Importantly, much of the variance in this ratio was related to differences in the ventral hippocampus to a greater extent than the dorsal hippocampus. The ratios of muscarinic receptors in the hippocampus relative to the basolateral amygdala also were lower in rats that preferred stimulus-response strategy over place strategy. Results confirm that learning strategy preference varies with biological sex in prepubertal rats with males biased toward a stimulus-response strategy, and that stimulus-response strategy is associated with lower ratios of muscarinic binding in the hippocampus relative to either the striatum or amygdala.
authors.affiliation: Department of Psychology, Tulane University, New Orleans, Louisiana 70118, USA. egrissom@tulane.edu
authors.forename: Elin M
authors.initials: EM
authors.lastname: Grissom
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Hawley
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Hodges
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Fawcett-Patel
authors.forename: Gary P
authors.initials: GP
authors.lastname: Dohanich
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008297:Male; D018782:Maze Learning; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011813:Quinuclidinyl Benzilate / Q000493:pharmacokinetics; D011869:Radioligand Assay; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012727:Sex Characteristics; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D014316:Tritium; D011813:Quinuclidinyl Benzilate
keywords: basolateral amygdala; cholinergic; dorsolateral striatum; hippocampus; sex differences