Renewal of appetitive behavior depends on the gonadal hormonal state of the female rat. In this experiment the effect of female rat estrous cycle stage on renewal of appetitive behaviors is replicated and extended upon to understand how endogenous hormonal states around the estrous cycle drive renewal at the neuronal population level. Estrous cycle stage (i.e., proestrus (P, high hormone) or metestrus/diestrus (M/D, low hormone)) was considered during two important learning and behavioral expression windows: at extinction training and during LTM/renewal testing. First, rats in P during context-dependent extinction training but in some other stage of the estrous cycle during long-term memory and renewal testing (Different) were shown to exhibit more renewal of conditioned foodcup (but not conditioned orienting) behavior compared to rats in other estrous cycle groups. Next, cellular compartment analysis of temporal activity using fluorescence in situ hybridization (catFISH) was used to examine immediate early gene activity of Arc mRNA in neuronal populations after distinct context-stimulus exposures (i.e., extinction and acquisition test contexts). Arc mRNA expression patterns were examined in the prefrontal cortex (PFC), amygdala, hippocampus (HPC), and paraventricular nucleus of the thalamus. P-different rats showed differential neuronal population activity in the infralimbic cortex of the PFC, the lateral amygdaloid nucleus, and both CA1 and CA3 regions of the dorsal HPC. In each region P-different rats exhibited more co-expression and less specificity of Arc mRNA compared to other hormonal groups, indicating that renewal of appetitive foodcup behavior induces Arc mRNA in overlapping neuronal populations in female rats.
IntroductionRenewal is a behavioral phenomenon wherein extinction learning fails to generalize between different contextual environments, thereby representing a significant challenge to extinction-based rehabilitative therapies. Previously, we have shown that renewal of extinguished appetitive behavior differs across the estrous cycle of the female rat. In this experiment that effect is replicated and extended upon to understand how the estrous cycle may modulate contextual representation at the neuronal population level to drive renewal.MethodsEstrous cycle stage [i.e., proestrus (P, high hormone) or metestrus/diestrus (M/D, low hormone)] was considered during two important learning and behavioral expression windows: at extinction training and during long-term memory (LTM)/renewal testing. Cellular compartment analysis of temporal activity using fluorescence in situ hybridization (catFISH) for Arc mRNA was conducted after the distinct context-stimulus exposures.ResultsRats in P during context-dependent extinction training but in a different stage of the estrous cycle during LTM and renewal testing (P-different) were shown to exhibit more renewal of conditioned foodcup (but not conditioned orienting) behavior compared to rats in other estrous cycle groups. Importantly, we discovered this depends on the order of tests. P-different rats showed differential Arc mRNA expression in regions of the prefrontal cortex (PFC), amygdala, and hippocampus (HPC). For each case P-different rats had more co-expression (i.e., expression of both nuclear and cytoplasmic) of Arc mRNA compared to other groups; specific to the dorsal HPC, P-different rats also had a more robust Arc mRNA response to the extinction context exposure.ConclusionThese data suggest female rats show estrous cycle state-dependent renewal of appetitive behavior, and differences in context and conditioned stimulus representation at the neuronal level may drive this effect.
Hormonal contraceptives (HCs) are commonly used among reproductive aged women and alter the physiological state of the user by interfering with endogenous hormone concentrations and their actions on the reproductive tract. As hormones such as estradiol and progesterone modulate the incidence of substance abuse disorders in women, it is important to consider the influence HCs have on the female brain and behavior. This experiment explores how female sex steroid hormonal states associated with the rat estrous cycle, and modulating those states with HCs, influences measures of drug preference and responsivity. First, rats underwent food-light Pavlovian conditioning to measure conditioned orienting, a known predictor of amphetamine (AMP) place preference. Then, rats were conditioned and tested for AMP place preference with either an HC-implant or during estrous cycle stages associated with different ovarian hormone levels (i.e., proestrus (P) or metestrus/diestrus (M/D)) while recording ultrasonic vocalizations (USVs) as an index of hedonic responsivity. Because of dopamine's (DA) role in modulation of AMP actions, DA cell activity and availability were examined using tyrosine hydroxylase and FOS immunohistochemistry after final AMP challenge. Conditioned orienting did not differ between cycling and HC-implanted. P rats emitted more USVs during conditioning, showed higher AMP place preference throughout testing, and had higher DA cell activity in the substantia nigra compared to M/D and HC-implanted rats. Sex steroid hormone serum concentration and uterine horn thickness predicted some but not all of these measures. This experiment suggests ovarian hormones affect drug preference and responsivity, while providing novel insight into how hormone-altering contraceptives may reduce these measures.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.