Normative Preclinical Algesiometry Data on the von Frey and Radiant Heat Paw-Withdrawal Tests: An Analysis of Data from More Than 8,000 Mice Over 20 Years.

The measurement of withdrawal to experimenter-delivered mechanical stimuli (von Frey test) and to heat stimuli (radiant heat paw-withdrawal or Hargreaves' test) applied to the hind paws is ubiquitous in preclinical pain research, but no normative values for the most-common applications of these tests have ever been published. We analyzed a retrospective data set of withdrawal thresholds or latencies in 8,150 mice in which these measures were taken using replicate determinations, before and after injection of inflammatory substances or experimental nerve damage producing pain hypersensitivity, totaling 97,332 measurements. All mice were tested in the same physical laboratory over a 20-year period using similar equipment and procedures. We nonetheless find evidence of large interindividual variability, affected by tester, genotype, mouse sex, tester sex, replicate order, and injury. These factors are discussed, and we believe that these normative data will serve as a useful reference for expected values in preclinical pain testing. PERSPECTIVE: This article presents a retrospective analysis of a large data set of mouse von Frey and radiant heat paw-withdrawal (Hargreaves' test) measurements collected in a single laboratory over 20 years. In addition to serving as a normative guide, sources of variability are identified including genotype, tester, and sex.

Biological sex influences the contribution of sign-tracking and anxiety-like behavior toward remifentanil self-administration.

Most people sample addictive drugs, but use becomes disordered in only a small minority. Two important factors that influence susceptibility to addiction are individual differences in personality traits and biological sex. The influence of traits on addiction-like behavior is well-characterized in preclinical models of cocaine self-administration, but less is understood in regards to opioids. How biological sex influences trait susceptibility to opioid self-administration is likewise less studied than psychostimulants. Thus, we sought to elucidate how biological sex and several addiction-relevant traits interact with the propensity to self-administer the opioid remifentanil. We first screened female (n = 19) and male (n = 19) rats for four addiction-relevant traits: impulsivity, novelty place-preference, anxiety-like behavior, and attribution of incentive value to reward cues. Rats were then trained to self-administer remifentanil in a "conflict model" of drug self-administration. Rats had to endure an electric shock to access the response manipulandum that triggered an intravenous infusion of remifentanil. In male rats, high anxiety-like behavior was positively correlated with the number of drug infusions if the shock level was low or completely absent. In females, sign-tracking was predictive of greater resistance to punishment during drug seeking; an effect that was mediated by anxiety-like behavior. Females consumed more remifentanil under all conditions, and their drug seeking persisted in the face of significantly greater current than males. These findings demonstrate that the influence of behavioral traits over the propensity to self-administer opioids is dependent upon biological sex. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Olfactory exposure to late-pregnant and lactating mice causes stress-induced analgesia in male mice.

In an attempt to improve reproducibility, more attention is being paid to potential sources of stress in the laboratory environment. Here, we report that the mere proximity of pregnant or lactating female mice causes olfactory-mediated stress-induced analgesia, to a variety of noxious stimuli, in gonadally intact male mice. We show that exposure to volatile compounds released in the urine of pregnant and lactating female mice can themselves produce stress and associated pain inhibition. This phenomenon, a novel form of female-to-male chemosignaling, is mediated by female scent marking of urinary volatiles, such as n-pentyl-acetate, and likely signals potential maternal aggression aimed at defending against infanticide by stranger males.

Attention to fat- and thin-related words in body-satisfied and body-dissatisfied women before and after thin model priming.

Understanding the cognitive processes underlying body dissatisfaction provides important information on the development and perpetuation of eating pathology. Previous research suggests that body-dissatisfied women process weight-related information differently than body-satisfied women, but the precise nature of these processing differences is not yet understood. In this study, eye-gaze tracking was used to measure attention to weight-related words in body-dissatisfied (n = 40) and body-satisfied (n = 38) women, before and after exposure to images of thin fashion models. Participants viewed 8-second displays containing fat-related, thin-related, and neutral words while their eye fixations were tracked and recorded. Based on previous research and theory, we predicted that body-dissatisfied women would attend to fat-related words more than body-satisfied women and would attend to thin-related words less. It was also predicted that exposure to thin model images would increase self-rated body dissatisfaction and heighten group differences in attention. The results indicated that body-dissatisfied women attended to both fat- and thin-related words more than body-satisfied women and that exposure to thin models did not increase this effect. Implications for cognitive models of eating disorders are discussed.

Early life adversity potentiates expression of addiction-related traits.

Many individuals sporadically and circumstantially sample addictive drugs, yet few become addicted. The individual vulnerabilities underlying the development of addiction are not well understood. Correlational findings show that early life adversity is associated with a greater propensity to develop drug addiction. However, the mechanisms by which early life adversity increases addiction vulnerability are unknown. Separate lines of research have found that several traits are associated with addiction. Here, we examined the effects of early life adversity on addiction-related traits in adulthood. We weaned male and female Sprague-Dawley rats (postnatal day - PND21) and randomly assigned them to either a non-adversity group (N-ADV) or an adversity group (ADV). ADV rats experienced adversity from PND 21-35, they were: a) singly housed, b) food restricted for 12h/day, c) subjected to forced-swim sessions, and d) restrained and exposed to predator odour (1h). As adults, rats were tested for impulsivity, anxiety-like behaviour, novelty preference, and attribution of incentive salience to a reward cue. ADV rats showed enhanced novelty preference and attributed greater incentive value to a reward cue. Compared to N-ADV rats, a greater proportion of ADV rats expressed multiple addiction risk traits. Furthermore, fewer ADV rats expressed no addiction risk traits. This effect was most evident in female ADV rats.