Sub-chronic stress induces similar behavioral effects in male and female mice despite sex-specific molecular adaptations in the nucleus accumbens.

Women are more likely than men to suffer from major depression and anxiety disorders, a fact that is thought to depend in part on sex differences in stress susceptibility. Consistent with this, several preclinical stress paradigms have been reported to exert differential effects in males vs. females. For example, several studies have reported that female rodents are susceptible to a subset of depression- and anxiety-like behaviors induced by six days of stress exposure while males remain largely resilient. The current study sought to evaluate the generalizability of this increased vulnerability of female mice to sub-chronic stressors by examining potential sex differences in response to a new five-day stress paradigm. In addition to measuring behavior, the current work also evaluated the effects of stress on the expression of several genes in the nucleus accumbens that have been suggested to underlie sex differences in behavioral responses to sub-chronic stress. The current results indicate that males and females exhibit mostly similar behavioral alterations after exposure to this new stress model, but several sex-specific molecular alterations were observed in the nucleus accumbens following stress. Overall, our data indicate that females do not exhibit a general increase in susceptibility to 'depression-' and 'anxiety-like' behaviors induced by sub-chronic stressors, and they could reflect an example of sexual convergence in which similar behavioral alterations occur in males and females despite sex-specific molecular changes.

Treatment of Articular Cartilage Defects of the Knee With Microfracture and Enhanced Microfracture Techniques.

Chondral injuries in the knee are a common source of pain and morbidity. Treatment of symptomatic chondral defects is challenging due to the limited healing capacity of articular cartilage. Microfracture is the most common surgical technique used to treat chondral defects in the knee and utilizes marrow stimulation to generate a fibrocartilage repair. Microfracture has demonstrated good short-term postoperative outcomes. Long-term outcomes following microfracture are variable, with loss of improvement attributed to the poor mechanical qualities of the fibrous repair tissue. Current research is focusing on ways to optimize the repair environment after microfracture using biological scaffolds (enhanced microfracture) to facilitate chondrogenic differentiation and proliferation to improve the quality of repair tissue.

Acute changes in glenohumeral range-of-motion following in-season minor league pitching starts.

BACKGROUND: Asymmetric glenohumeral range-of-motion (ROM) between the throwing and non-throwing arms of overhead athletes has been well described in the literature. Thresholds of internal rotation (IR) loss have been associated with throwing arm injury in baseball players. Acute changes in shoulder ROM following an individual pitching appearance remain poorly understood. OBJECTIVES: To determine the acute change of external rotation (ER), IR, and total arc-of-motion (TAM) in minor league starting pitchers immediately following an in-season starting pitching appearance. METHODS: Nine minor league starting pitchers participated in the study with data collected for 22 individual starts. IR, ER and TAM were measured in the throwing shoulder and non-throwing shoulder at three time points for each appearance: before, immediately following, and at 24 hours following the pitching appearance. RESULTS: In the throwing arm, IR significantly decreased (49.4 vs 46.0, p = 0.037) immediately after pitching, and ER significantly increased immediately following an appearance (150.7 vs 153.6, p = 0.030) and at 24 hours (150.7 vs 154.0, p = 0.028). No difference was detected in throwing arm TAM and IR at 24 hours, or TAM immediately following an appearance. CONCLUSIONS: Minor league pitchers demonstrate the dynamic glenohumeral ROM changes after starting appearances of increased ER and diminished IR with maintenance of TAM. At 24 hours, the observed loss of IR had resolved, whereas the gains in ER remained present. Our study supports the need to further assess the acute changes of glenohumeral ROM in pitchers, and the association of acute glenohumeral ROM change with the development of pathologic ROM profiles and injury.

Potentiation of cocaine-primed reinstatement of drug seeking in female rats during estrus.

RATIONALE: Gender differences exist in the patterns of drug taking in cocaine addiction, suggesting that the propensity to relapse varies between men and women. Previous reports have shown sex differences in both cocaine-primed and conditioned-cued reinstatement of cocaine-seeking behavior, including recent evidence that the estrous cycle influences the level of conditioned-cued reinstatement. However, the influence of the estrous cycle on cocaine-primed reinstatement has not been examined. OBJECTIVE: Accordingly, we assessed the influence of sex and estrous cycle status on cocaine-primed reinstatement of drug-seeking behavior in Sprague-Dawley rats. METHODS: Intact male and female rats were trained to lever press to self-administer intravenous cocaine (0.5 mg/kg every infusion; fixed ratio 1, 20-s time-out following each infusion), followed by prolonged extinction training, and subsequently tested for the ability of a cocaine-priming injection (0, 5, or 10 mg/kg i.p.) to reinstate extinguished cocaine seeking (i.e., nonreinforced lever responding). RESULTS: Despite no differences in cocaine intake between male and female rats, females responded more on the cocaine-paired lever during self-administration and extinction relative to males. Subsequently, both males and females exhibited a dose-dependent cocaine-primed reinstatement of extinguished drug-seeking behavior. Moreover, females in estrus exhibited significantly higher reinstatement than either males or non-estrus females, following a high-dose (10 mg/kg) cocaine prime. CONCLUSIONS: Estrus females display heightened sensitivity to the motivational and/or stimulant effects of cocaine, suggesting that hormonal state modulates drug craving and propensity for drug relapse in cocaine addicts.

Influence of sex and estrous cyclicity on conditioned cue-induced reinstatement of cocaine-seeking behavior in rats.

RATIONALE: Sex differences have been reported in physiological and behavioral responses to cocaine, but it is unclear whether sex differences exist in conditioned-cued relapse to cocaine seeking after prolonged abstinence. Furthermore, the role of estrous cyclicity in conditioned-cued relapse has not been investigated. OBJECTIVE: We assessed the influence of sex and estrous cyclicity on conditioned-cued reinstatement of drug-seeking behavior in Sprague-Dawley rats. METHODS: Rats were trained to self-administer intravenous cocaine (unconditioned stimulus, US; 0.25, 0.4, 0.5, 0.6, or 1.0 mg/kg per infusion) paired with light+tone conditioned stimuli (CSs) and were subsequently tested for the ability of the CSs to reinstate extinguished cocaine seeking (i.e., nonreinforced lever responding). RESULTS: Females exhibited more responding on the cocaine-paired lever during self-administration and extinction than males. Subsequently, males exhibited equally robust conditioned-cued reinstatement of extinguished drug-seeking behavior independent of cocaine training dose. Males and females trained on 0.4-0.6 mg/kg cocaine reinstated to a similar extent. However, females trained on the lowest dose (0.25 mg/kg) exhibited less reinstatement than males, and the source of this effect was the absence of reinstatement in estrous females. In addition, independent of estrous state, females trained on the highest dose (1.0 mg/kg) exhibited less reinstatement than males. CONCLUSIONS: While males and females are equally responsive to cocaine-paired CSs when the conditions for CS-US association are optimal, females appear to attribute less motivational significance to the CS when it presumably acquires weaker motivational salience because of (a) a low cocaine dose or (b) weaker CS-US contiguity due to the prolonged effects of a high cocaine dose.

The role of the dorsomedial prefrontal cortex, basolateral amygdala, and dorsal hippocampus in contextual reinstatement of cocaine seeking in rats.

The present study tested the hypothesis that separate neural substrates mediate cocaine relapse elicited by drug-associated contextual stimuli vs explicit conditioned stimuli (CSs) and cocaine. Specifically, we investigated the involvement of the dorsal hippocampus (DH), basolateral amygdala (BLA), and dorsomedial prefrontal cortex (dmPFC) in contextual reinstatement of cocaine-seeking behavior and the involvement of the DH in explicit CS- and cocaine-induced reinstatement. Rats were trained to self-administer cocaine in a distinct context or in the presence of CSs paired explicitly with cocaine infusions. Responding of context-trained rats was then extinguished in the previously cocaine-paired or an alternate context, whereas responding of explicit CS-trained rats was extinguished in the absence of the CSs. Subsequently, the target brain regions or anatomical control regions were functionally inactivated using tetrodotoxin (0 or 5 ng/side), and cocaine-seeking behavior (ie, nonreinforced responses) was assessed in the cocaine-paired context, in the alternate context, in the presence of the explicit CSs, or following cocaine priming (10 mg/kg, i.p.). DH inactivation abolished contextual, but failed to alter explicit CS- or cocaine-induced, reinstatement of cocaine-seeking behavior. BLA or dmPFC inactivation also abolished contextual reinstatement. Conversely, inactivation of the control brain regions failed to alter contextual reinstatement. In conclusion, the DH, BLA, and dmPFC play critical roles in contextual reinstatement. Previous findings suggest that the BLA is critical for explicit CS-induced, but not cocaine-primed, reinstatement and the dmPFC is critical for both explicit CS-induced and cocaine-primed reinstatement. Thus, distinct but partially overlapping neural substrates mediate context-induced, explicit CS-induced, and cocaine-primed reinstatement of extinguished cocaine-seeking behavior.