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Rationale: Voluntary aerobic exercise has shown promise as a treatment for substance abuse, reducing relapse in cocaine-dependent people. Wheel running also attenuates drug-primed and cue-induced reinstatement of cocaine seeking in rats, an animal model of relapse. However, in most of these studies, wheel access was provided throughout cocaine self-administration and/or extinction and had effects on several parameters of drug seeking. Moreover, the effects of exercise on footshock stress-induced reinstatement have not been investigated., Objectives: The purposes of this study were to isolate and specifically examine the protective effect of exercise on relapse-like behavior elicited by a drug prime or stress., Methods: Rats were trained to self-administer cocaine at a stable level, followed by extinction training. Once extinction criteria were met, rats were split into exercise (24 h, continuous access to running wheel) and sedentary groups for 3 weeks, after which, drug-seeking behavior was assessed following a cocaine prime or footshock. We also measured galanin messenger RNA (mRNA) in the locus coeruleus and A2 noradrenergic nucleus., Results: Exercising rats ran ∼4-6 km/day, comparable to levels previously reported for rats without a history of cocaine self-administration. Post-extinction exercise significantly attenuated cocaine-primed, but not footshock stress-induced, reinstatement of cocaine seeking, and increased galanin mRNA expression in the LC but not A2., Conclusion: These results indicate that chronic wheel running can attenuate some forms of reinstatement, even when initiated after the cessation of cocaine self-administration, supporting the idea that voluntary exercise programs may help maintain abstinence in clinical populations.

Previous research has demonstrated that low doses of anxiogenic central benzodiazepine receptor (CBR) ligands, the beta-carbolines, improve performance in various learning and memory tests in animals if administered prior to training. The present experiments compared the effect of a beta-carboline (FG 7142) with that of a pharmacologically distinct anxiogenic compound, a peripheral benzodiazepine receptor (PBR) ligand, 4'-chlorodiazepam (Ro5-4864), in two tests of learning and memory in rats. As expected, FG 7142 significantly improved performance in a passive avoidance test. Ro5-4864 was without effect. In a shuttlebox escape test, Ro5-4864 significantly impaired performance while FG 7142 had no effect. The effect of Ro5-4864 was antagonized by the specific peripheral benzodiazepine receptor antagonist, PK 11195. These results indicate that the differential impact of CBR and PBR anxiogenic ligands on performance in aversively-motivated learning tests may be a reflection of their distinct pharmacologies.

Ovulation was induced in rabbits by intravenous administration of human chorionic gonadotrophin (HCG), and 4-5 h later the ovaries were isolated and introduced into an in-vitro perfusion system containing synthetic medium with albumin. Rupture of follicles occurred in vitro within the physiological time range (mean 11.3 h after injection of HCG), although with a reduced frequency. Preovulatory and ruptured follicles were studied in detail by light and electron microscopy. In the granulosa layer of ruptured or preovulatory follicles cytoplasmic blebbing activity, disappearance of Call-Exner bodies and differentiation toward luteinized cells were found. Perhaps the most important sign of normal preovulatory development in vitro was that the basement membrane surrounding the granulosa layer was penetrated by projections of granulosa cells. In the absence of this penetration phenomenon the granulosa layer prolapsed out of the follicle. Immediately before rupture, follicles showed marked degeneration, restricted to the outer layers of the apical wall, which is compatible with the hypothesis that degradative enzymes are released close to the surface of preovulatory follicles. Although the majority of follicles that ovulated under in-vitro conditions showed the same kind of morphological alterations as can be seen in vivo, occasional atypical ruptures occurred without any overt signs during perfusion. Also technical manipulations of the perfusion system, e.g., nonphysiological increase of perfusion pressure, could force follicles to rupture. This illustrates the importance of careful morphological study of all ovaries perfused in vitro before conclusions are drawn.

Isolated ovaries from untreated, sexually mature rabbits were introduced into an in vitro perfusion system and perfused with a chemically defined medium containing albumin. The ovaries were perfused for up to 15 h (mean 11.5 h) and then processed for morphological investigation. Both at the light- and electron-microscopical levels, most of the ovaries exhibited a normal structure comparable with ovaries in situ. In two cases, however, marked accumulations of bacteria were found, although not inside the follicles. Since ovulation in the rabbit normally occurs between 9.5-13 h after mating or human chorionic gonadotrophin treatment, this model seems adequate for studies of ovulation in vitro. It is, however, important to study the ovaries microscopically after the perfusion to detect artifacts, e.g., bacterial infection, that may have influence on the process of ovulation.