Sexual behavior induction of c-Fos in the nucleus accumbens and amphetamine-stimulated locomotor activity are sensitized by previous sexual experience in female Syrian hamsters.

Dopamine transmission in the nucleus accumbens can be activated by drugs, stress, or motivated behaviors, and repeated exposure to these stimuli can sensitize this dopamine response. The objectives of this study were to determine whether female sexual behavior activates nucleus accumbens neurons and whether past sexual experience cross-sensitizes neuronal responses in the nucleus accumbens to amphetamine. Using immunocytochemical labeling, c-Fos expression in different subregions (shell vs core at the rostral, middle, and caudal levels) of the nucleus accumbens was examined in female hamsters that had varying amounts of sexual experience. Female hamsters, given either 6 weeks of sexual experience or remaining sexually naive, were tested for sexual behavior by exposure to adult male hamsters. Previous sexual experience increased c-Fos labeling in the rostral and caudal levels but not in the middle levels of the nucleus accumbens. Testing for sexual behavior increased labeling in the core, but not the shell, of the nucleus accumbens. To validate that female sexual behavior can sensitize neurons in the mesolimbic dopamine pathway, the locomotor responses of sexually experienced and sexually naive females to an amphetamine injection were then compared. Amphetamine increased general locomotor activity in all females. However, sexually experienced animals responded sooner to amphetamine than did sexually naive animals. These data indicate that female sexual behavior can activate neurons in the nucleus accumbens and that sexual experience can cross-sensitize neuronal responses to amphetamine. In addition, these results provide additional evidence for functional differences between the shell and core of the nucleus accumbens and across its anteroposterior axis.

Changes in gene expression within the nucleus accumbens and striatum following sexual experience.

Sexual experience, like repeated drug use, produces long-term changes including sensitization in the nucleus accumbens and dorsal striatum. To better understand the molecular mechanisms underlying the neuroadaptations following sexual experience, we employed a DNA microarray approach to identify genes differentially expressed between sexually experienced and sexually naive female hamsters within the nucleus accumbens and dorsal striatum. For 6 weeks, a stimulus male was placed in the home cage of one-half of the hormonally primed, ovariectomized female hamsters. On the seventh week, the two experimental groups were subdivided, with one half paired with a stimulus male. In comparison with sexually naive animals, sexually experienced hamsters receiving a stimulus male on week 7 exhibited an increase in a large number of genes. Conversely, sexually experienced female hamsters not receiving a stimulus male on week 7 exhibited a reduction in the expression of many genes. For directional changes and the categories of genes regulated by the experimental conditions, data were consistent across the nucleus accumbens and dorsal striatum. However, the specific genes exhibiting changes in expression were disparate. These experiments, among the first to profile genes regulated by female sexual behavior, will provide insight into the mechanisms by which both motivated behaviors and drugs of abuse induce long-term changes in the mesolimbic and nigrostriatal dopamine pathways.

Localization of protein Ser/Thr phosphatase 5 in rat brain.

Protein phosphatase 5 is a recently discovered Ser/Thr phosphatase that is structurally related to calcineurin and protein phosphatases 1 and 2. Northern blot and in situ hybridization studies have shown that protein phosphatase 5 mRNA is present at high levels in brain and is localized to discrete regions. In the present study, we used immunocytochemistry and immunoblot analyses to examine the regional and subcellular distribution of this enzyme in brain. Our work demonstrates that protein phosphatase 5 is widely expressed throughout brain, but is not uniformly distributed. The most intense staining occurred in neurons of the cerebellum, cerebral cortex, and the supraoptic nucleus of the hypothalamus. Other areas also contained immunoreactive cell bodies, including the globus pallidus, hippocampus, thalamus, lateral preoptic area of the hypothalamus, substantia nigra and other brainstem nuclei. Staining in these cells was observed primarily in perikarya and proximal processes.

Cerebrospinal fluid pressure.

The cerebrospinal fluid pressure at the foramen of Monro in man in the recumbent position is less than 100 mm water relative to atmospheric pressure. The oscillations in the pressure wave due to respiration and cardiac pulsation vary with the actual pressure and increase as the overall pressure rises. In man lying horizontally the oscillation at the foramen of Monro is usually less than 50 mm water pressure, of which the cardiac component is about 15 mm and the respiratory component 35 mm water pressure. The fluid pressure within the cranial cavity is not uniform. In the recumbent face upwards position the pressure at the frontal pole is close to atmospheric or slightly subatmospheric but at the occipital pole is of the order of 160 to 190 mm water pressure. Examples are given showing the effect of posture on cerebrospinal fluid pressures in man and in the goat. The concentration of arachnoid granulations and venous lacunae near the vertex and the pressures in this region are discussed. The need for more precise methods of pressure measurement in the superior sagittal sinus is outlined by citing the Pitot tube. Pressure studies on patients with presenile dementia and dilated cerebral ventricles are reported.

Open label trial of coenzyme Q10 as a migraine preventive.

The objective was to assess the efficacy of coenzyme Q10 as a preventive treatment for migraine headaches. Thirty-two patients (26 women, 6 men) with a history of episodic migraine with or without aura were treated with coenzyme Q10 at a dose of 150 mg per day. Thirty-one of 32 patients completed the study; 61.3% of patients had a greater than 50% reduction in number of days with migraine headache. The average number of days with migraine during the baseline period was 7.34 and this decreased to 2.95 after 3 months of therapy, which was a statistically significant response (P < 0.0001). Mean reduction in migraine frequency after 1 month of treatment was 13.1% and this increased to 55.3% by the end of 3 months. Mean migraine attack frequency was 4.85 during the baseline period and this decreased to 2.81 attacks by the end of the study period, which was a statistically significant response (P < 0.001). There were no side-effects noted with coenzyme Q10. From this open label investigation coenzyme Q10 appears to be a good migraine preventive. Placebo-controlled trials are now necessary to determine the true efficacy of coenzyme Q10 in migraine prevention.