The influence of sex and estrous cyclicity on cocaine and remifentanil demand in rats. 2020

Ryan T Lacy, and Bridget P Austin, and Justin C Strickland
Department of Psychology, Franklin & Marshall College, Lancaster, PA, USA.

The application of behavioral economic demand theory in addiction science has proved useful for evaluating individual characteristics underlying abuse liability. Two factors that have received comparably little attention within this literature are sex and gonadal hormones. We determined cocaine and remifentanil demand in male and female rats using a within-session procedure. Cocaine and remifentanil demand were evaluated for 15 consecutive days using a balanced, crossover design that randomized drug order. This design allowed for the evaluation of temporal and exposure effects on two independent dimensions of demand, unconstrained demand (Q0 ) and demand elasticity (α). Estrous cyclicity was tracked to determine the contribution of phase to demand. No overall sex differences were observed. Increased unconstrained demand for cocaine and remifentanil was observed in females during periods in which estrogen was high (eg, estrus phase). Unconstrained remifentanil demand escalated over the 15-day testing period, but escalation was not observed for cocaine or for demand elasticity. A significant exposure effect was also observed in which greater prior remifentanil intake increased unconstrained cocaine demand and reduced cocaine demand elasticity. These effects were directionally specific as no significant effects of prior cocaine exposure were observed on remifentanil demand measures. These data suggest that unconstrained demand and demand elasticity do not differ between male and female subjects; however, that unconstrained demand is associated with estrous cyclicity. These findings also suggest that opioid exposure enhances subsequent demand for psychomotor stimulants, which may be important when considering recent increases in nonmedical prescription opioid use in the United States.

UI MeSH Term Description Entries
D008297 Male Males
D003042 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females
D000077208 Remifentanil A piperidine-propionate derivative and opioid analgesic structurally related to FENTANYL. It functions as a short-acting MU OPIOID RECEPTOR agonist, and is used as an analgesic during induction or maintenance of general anesthesia, following surgery, during childbirth, and in mechanically ventilated patients under intensive care. 3-(4-Methoxycarbonyl-4-((1-oxopropyl)phenylamino)-1-piperidine)propanoic Acid Methyl Ester,GI 87084B,GI-87084B,GI87084B,Remifentanil Hydrochloride,Remifentanil Monohydrochloride,Ultiva
D000701 Analgesics, Opioid Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. Opioid,Opioid Analgesic,Opioid Analgesics,Opioids,Full Opioid Agonists,Opioid Full Agonists,Opioid Mixed Agonist-Antagonists,Opioid Partial Agonists,Partial Opioid Agonists,Agonist-Antagonists, Opioid Mixed,Agonists, Full Opioid,Agonists, Opioid Full,Agonists, Opioid Partial,Agonists, Partial Opioid,Analgesic, Opioid,Full Agonists, Opioid,Mixed Agonist-Antagonists, Opioid,Opioid Agonists, Full,Opioid Agonists, Partial,Opioid Mixed Agonist Antagonists,Partial Agonists, Opioid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D012646 Self Administration Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. Administration, Self,Administrations, Self,Self Administrations
D012737 Sex Factors Maleness or femaleness as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or effect of a circumstance. It is used with human or animal concepts but should be differentiated from SEX CHARACTERISTICS, anatomical or physiological manifestations of sex, and from SEX DISTRIBUTION, the number of males and females in given circumstances. Factor, Sex,Factors, Sex,Sex Factor

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