Generalization of a positive-feature interoceptive morphine occasion setter across the rat estrous cycle

Davin R Peart; Ella V Claridge; Jessica M Karlovcec; Rita El Azali; Kathleen E LaDouceur; Anita Sikic; Abina Thomas; Adiia P Stone; Jennifer E Murray

doi:10.1016/j.yhbeh.2024.105541

Generalization of a positive-feature interoceptive morphine occasion setter across the rat estrous cycle

Horm Behav. 2024 Apr 6:162:105541. doi: 10.1016/j.yhbeh.2024.105541. Online ahead of print.

Authors

Davin R Peart¹, Ella V Claridge², Jessica M Karlovcec¹, Rita El Azali¹, Kathleen E LaDouceur¹, Anita Sikic¹, Abina Thomas², Adiia P Stone¹, Jennifer E Murray³

Affiliations

¹ Department of Psychology, University of Guelph, Guelph, ON, Canada; Collaborative Neurosciences Graduate Program, University of Guelph, Guelph, ON, Canada.
² Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada.
³ Department of Psychology, University of Guelph, Guelph, ON, Canada; Collaborative Neurosciences Graduate Program, University of Guelph, Guelph, ON, Canada. Electronic address: jmurr@uoguelph.ca.

PMID: 38583235
DOI: 10.1016/j.yhbeh.2024.105541

Abstract

Introduction: Interoceptive stimuli elicited by drug administration acquire conditioned modulatory properties of the induction of conditioned appetitive behaviours by exteroceptive cues. This effect may be modeled using a drug discrimination task in which the drug stimulus is trained as a positive-feature (FP) occasion setter (OS) that disambiguates the relation between an exteroceptive light conditioned stimulus (CS) and a sucrose unconditioned stimulus (US). We previously reported that females are less sensitive to generalization of a FP morphine OS than males, so we investigated the role of endogenous ovarian hormones in this difference.

Methods: Male and female rats received intermixed injections of 3.2 mg/kg morphine or saline before each daily training session. Training consisted of 8 presentations of the CS, each followed by access to sucrose on morphine, but not saline sessions. Following acquisiton, rats were tested for generalization of the morphine stimulus to 0, 1.0, 3.2, and 5.4 mg/kg morphine. Female rats were monitored for estrous cyclicity using vaginal cytology throughout the study.

Results: Both sexes acquired stable drug discrimination. A gradient of generalization was measured across morphine doses and this behaviour did not differ by sex, nor did it differ across the estrous cycle in females.

Conclusions: Morphine generalization is independent of fluctuations in levels of sex and endogenous gonadal hormones in females under these experimental conditions.

Keywords: Estrous cycle; Female rats; Freely cycling; Generalization; Learning; Morphine; Occasion setting; Opioids; Pavlovian drug discrimination; Sex differences.