Puberty and shifting values (Commentary on Bell et al .)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96344/1/ejn12073.pd

The federal plan for health science and technology’s response to the opioid crisis: understanding sex and gender differences as part of the solution is overlooked

Abstract The Fast-Track Action Committee on (the) Health Science and Technology Response to the Opioid Crisis recently released their draft report for public comment. This report provides the “roadmap” for a coordinated federal research and development response to the opioid crisis. Other than noting the important concerns regarding maternal and neonatal exposure to opioids, the report overlooks the laboratory, clinical, and epidemiological data that inform the need for further research on sex and gender differences in opioid addiction that have critical gender-based treatment and prevention implications. As we embark on research and development, investigations into the neurobiology of pain, opioid use, and addiction must include both females and males in model systems and, similarly, psychological and sociocultural investigations must study women and men. All data should be reported by sex and gender so that gender-specific treatment and prevention strategies derived from this research are provided to practitioners and the public. We encourage biomedical researchers and clinical care providers, as well as the public, to insist that a successful response to the opioid crisis should highlight the importance of understanding sex and gender differences in the current opioid epidemic.https://deepblue.lib.umich.edu/bitstream/2027.42/146784/1/13293_2018_Article_215.pd

Effects of Nerve Growth Factor Infusion on Behavioral Recovery and Graft Survival Following Intraventricular Adrenal Medulla Grafts in the Unilateral 6-Hydroxydopamine Lesioned Rat

NGF was infused into the lateral ventricle of rats with unilateral 6-OHDA lesions of the substantia nigra along with adrenal medulla or control grafts. Treatment effectiveness, as measured by amphetamine-induced turning behavior, indicated that there were no significant differences between treated and control groups in spite of the survival of tyrosine hydroxylase (TH) immunoreactive grafts. Furthermore, adrenal medulla graft survival was not dependent on NGF infusion. These results indicate that TH-posttive graft survival is not correlated with behavioral recovery as assessed by amphetamine-induced turning. These results differ from studies which utilized apomorphineinduced turning as a measure of behavioral recovery. We propose that adrenal medulla graft survival alone is not sufficient to promote behavioral recovery in the 6-OHDA lesioned rat

Sociocultural context for sex differences in addiction

In this review, we discuss the importance of investigating both sex and gender differences in addiction and relapse in studies of humans and in animal models. Addiction is both a cultural and biological phenomenon. Sex and gender differences are not solely determined by our biology, nor are they entirely cultural; they are interactions between biology and the environment that are continuously played out throughout development. Lessons from the historical record illustrate how context and attitudes affect the way that substance use in men and women is regarded. Finally, cultural and environmental influences may differentially affect men and women, and affect how they respond to drugs of abuse and to treatment protocols. We recommend that both animal models and clinical research need to be developed to consider how contextual and social factors may influence the biological processes of addiction and relapse differentially in men and women.Addiction is both a cultural and biological phenomenon and interactions between biology and the environment are continuously played out throughout development. Lessons from the historical record illustrate how context and attitudes affect the way that substance abuse and treatment can differentially affect men and women. Animal models and clinical research need to consider how contextual and social factors may influence the biological processes of addiction and relapse differentially in males and females.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133600/1/adb12383.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133600/2/adb12383_am.pd

Female rats are not more variable than male rats: a meta-analysis of neuroscience studies

Abstract Background Not including female rats or mice in neuroscience research has been justified due to the variable nature of female data caused by hormonal fluctuations associated with the female reproductive cycle. In this study, we investigated whether female rats are more variable than male rats in scientific reports of neuroscience-related traits. Methods PubMed and Web of Science were searched for the period from August 1, 2010, to July 31, 2014, for articles that included both male and female rats and that measured diverse aspects of brain function. Only empirical articles using both male and female gonad-intact adult rats, written in English, and including the number of subjects (or a range) were included. This resulted in 311 articles for analysis. Data were extracted from digital images from article PDFs and from manuscript tables and text. The mean and standard deviation (SD) were determined for each data point and their quotient provided a coefficient of variation (CV) as a measure of trait-specific variability for each sex. Additionally, the results were coded for the type of research being measured (behavior, electrophysiology, histology, neurochemistry, and non-brain measures) and for the strain of rat. Over 6000 data points were extracted for both males and females. Subsets of the data were coded for whether male and female mean values differed significantly and whether animals were grouped or individually housed. Results Across all traits, there were no sex differences in trait variability, as indicated by the CV, and there were no sex differences in any of the four neuroscience categories, even in instances in which mean values for males and females were significantly different. Female rats were not more variable at any stage of the estrous cycle than male rats. There were no sex differences in the effect of housing conditions on CV. On one of four measures of non-brain function, females were more variable than males. Conclusions We conclude that even when female rats are used in neuroscience experiments without regard to the estrous cycle stage, their data are not more variable than those of male rats. This is true for behavioral, electrophysiological, neurochemical, and histological measures. Thus, when designing neuroscience experiments to include both male and female rats, power analyses based on variance in male measures are sufficient to yield accurate numbers for females as well, even when the estrous cycle is not taken into consideration.http://deepblue.lib.umich.edu/bitstream/2027.42/134612/1/13293_2016_Article_87.pd

Quantitative microdialysis determination of extracellular striatal dopamine concentration in male and female rats: effects of estrous cycle and gonadectomy

Sex differences in basal extracellular striatal dopamine concentrations in gonadectomized male and female rats have been reported previously. In the current experiment, estrous cycle-dependent variation, sex differences and the effect of gonadectomy on extracellular striatal dopamine concentrations were determined using quantitative microdialysis. Female rats were found to have significantly higher extracellular striatal dopamine concentrations in proestrus and estrus than in diestrus or after ovariectomy. In contrast, castration of male rats had no effect on extracellular striatal dopamine concentrations. Thus, endogenous ovarian hormones, but not testicular hormones, modulate extracellular striatal dopamine concentrations in rats.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31250/1/0000156.pd

Adrenal medulla grafts enhance functional activity of the striatal dopamine system following substantia nigra lesions

Adrenal medulla grafts in the lateral ventricle reduce the behavioral manifestations of striatal dopamine depletion in an animal model of Parkinson's disease. Using microdialysis in freely moving rats, the present experiments determined that dopamine was not detectable in cerebrospinal fluid (CSF). However, adrenal medulla grafts were associated with an increase in dopamine turnover and amphetamine-stimulated striatal dopamine release was increased in animals with behaviorally effective adrenal medulla grafts. Therefore, adrenal medulla grafts increase striatal dopamine activity without an appreciable release of dopamine into the CSF. Adrenal medulla grafts also increased serum dopamine concentrations, and the increase in serum dopamine was directly correlated with the behavioral efficacy of the grafts. We suggest that dopamine, produced by adrenal medulla grafts, may gain access to the striatum via the blood supply and then leak out into the host striatum through permeable blood vessels adjacent to the graft. Through this mechanism, adrenal medulla grafts may increase functional dopaminergic activity in the striatum. These results may be important for understanding how autografts of adrenal medulla cells produce a putative alleviation of the symptoms of Parkinson's disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27095/1/0000086.pd

Changes in blood-brain barrier permeability are associated with behavioral and neurochemical indices of recovery following intraventricular adrenal medulla grafts in an animal model of parkinson's disease

Intraventricular adrenal medulla grafts were found to produce dissociable effects on rotational behavior induced by amphetamine and apomorphine in rats with unilateral striatal dopamine depletions. Some animals showed a decrease in the behavioral response to apomorphine, some showed a decrease to amphetamine, and some showed a decrease to both amphetamine and apomorphine. Using in vivo microdialysis, the experiments reported demonstrate that in animals with decreased rotational behavior, assessed with either amphetamine or apomorphine, there was an increase in the permeability of the blood-brain barrier to dopamine. The increased blood-brain barrier permeability was visually confirmed with horseradish peroxidase. The extent of the blood-brain barrier disruption, however, was greater in animals with a decreased response to amphetamine. Animals that exhibited decreased amphetamine-induced turning after adrenal medulla grafts also had a greater amphetamine-stimulated increase in striatal dopamine and greater extracellular striatal dihydroxyphenylacetic acid concentrations compared to controls and animals with a graft-induced decrease in the response to apomorphine. We conclude that more than one mechanism is involved in mediating the behavioral effects of adrenal medulla grafts.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29050/1/0000083.pd

The influence of estrogen on nigrostriatal dopamine activity : Behavioral and neurochemical evidence for both pre- and postsynaptic components

The results of 3 experiments examining the influence of estrogen on the nigrostriatal dopamine (DA) system are reported. In two experiments the influence of hormonal manipulations on amphetamine (AMPH)-induced rotational behavior was investigated using rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. It was found that: (1) female rats in estrus make more rotations than ovariectomized (OVX) rats; and (2) estrogen treatment (5 [mu]g estradiol benzoate, daily for 4 days) in OVX rats enhances AMPH-induced rotational behavior 4 h and 4 days after estrogen treatment. During the intervening period, at 24 h after cessation of estrogen treatment, control and hormone-treated animals did not differ. In a third experiment, the effect of estrogen treatment on the release of endogenous DA from striatal tissue slices in superfusion was examined. Estrogen enhanced AMPH-stimulated striatal DA release 4 h after the last treatment relative to OVX controls. However, 24 h and 4 days after estrogen treatment DA release had returned to control levels. It is suggested that estrogen has an immediate potentiating effect on striatal DA release, and this may be responsible for the increased behavioral response to AMPH 4 h after estrogen treatment. The previously demonstrated increase in postsynaptic striatal DA receptors may be responsible for the second increase in AMPH-induced rotational behavior, that occurs 4 days after estrogen treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26324/1/0000411.pd

Behavioral sensitization is accompanied by an enhancement in amphetamine-stimulated dopamine release from striatal tissue in vitro

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23802/1/0000040.pd