Antidepressant-like effects of acupuncture via modulation of corticosterone, sex hormones, and hippocampal BDNF expression in male rats.

BACKGROUND: Post-weaning social isolated rodents exhibit pathophysiological changes associated with depression including adrenal axis hyperactivity, gonadal hormone level disturbances, molecular alterations in hippocampus, and immobility behavior in the forced swimming test (FST). Although acupuncture by absorbable thread implantation (acu-catgut, AC) elicits antidepressant-like effects in social isolated rats, AC effects on neuroendocrine and hippocampal molecular alterations have been less characterized. OBJECTIVE: To investigate the participation of gonadal hormones, corticosterone, and brain-derived neurotrophic factor (BDNF) hippocampal expression, on the AC antidepressant-like effects in social isolated male rats. METHODS: Sprague-Dawley male rats were raised in social isolation (SI) or standard conditions, for 11 weeks. AC (on Baihui (Du20), Yintang (E X-HN3), Shenshu (BL 23), Pishu (BL 20), Ganshu (BL 18), Xinshu (BL 15) and Guanyuan (Ren 4)), or Sham-AC (puncturing of acupoints without embedding the thread), was applied during the last three weeks of isolation period. Rats were evaluated in the FST; hormones plasmatic levels and hippocampal BDNF content were quantified by ELISA and Western blotting, respectively. RESULTS: Social isolated rats showed more immobility in the FST and had lower testosterone and estradiol levels, higher corticosterone levels, and reduced hippocampal BDNF content than controls. BDNF level in hippocampus inversely correlated to depression-like behavior. AC but not sham-AC normalized immobility behavior, steroid hormone levels, and BDNF content, as in rats raised in a social environment. CONCLUSIONS: AC antidepressant effect could be related to an improvement of hippocampal BDNF protein expression, as well as corticosterone and sex hormones disturbances associated with prolonged exposure to stress caused by social isolation. Present findings have implications for depression treatment in individuals early exposed to stress.

Calea zacatechichi Schltdl. (Compositae) produces anxiolytic- and antidepressant-like effects, and increases the hippocampal activity during REM sleep in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Calea zacatechichi is a plant with an extensive popular and ritual use in Mexico. In healthy volunteers, it induces well-being and tranquility senses, and facilitates superficial stages of sleep. However, anxiolytic, and antidepressant-like effects and changes on the sleep-waking stages have not been explored. AIM: To determine anxiolytic and antidepressant-like effects of an aqueous extract of C. zacatechichi (CZ) in rodents and to analyze their effects on hippocampal activity in the rat sleep-waking cycle. MATERIAL AND METHODS: CZ anxiolytic- and antidepressant-like effects were evaluated in several mice and rat behavioral paradigms. CZ effects on temporal distribution of sleep were described, and hippocampus EEG frequency patterns were analyzed during the sleep-waking cycle; absolute and relative powers were analyzed during Rapid Eye Movements (REM) and non-REM sleep stages. CZ chemical analysis was performed by UPLC-ESI-MS. RESULTS: CZ produced specific and robust anxiolytic- and antidepressant-like effects in mice and rats, similar to those of prototypical drugs, at doses ranging from 0.5 to 50 mg/kg. CZ at 100 mg/kg produced visible mild sedative effects in rats, associated with a significant increase in Slow Wave Sleep episodes during a 6 h recording, and enhanced fast frequencies of hippocampus (gamma-band:31-50 Hz) during REM sleep. CONCLUSION: Results could support the well-being and tranquility senses reported by healthy consumers, and to explain the oneiric content during dreams and some improvements in cognitive processes described by consumers. Anxiolytic- and antidepressant-like effects of this species, reported for first time in this study could improve some aspects of mental health.

Piper auritum Kunth (Piperaceae) improves the sexual performance of sluggish male rats through enhancing ejaculation.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper auritum Kunth is employed as an aphrodisiac in the traditional medicine, but corroborative evidence for such effect is scarce. AIM OF THE STUDY: The pro-sexual effect of an aqueous extract of P. auritum and its possible mechanisms were analyzed in two paradigms of male sexual function. MATERIAL AND METHODS: Effects of an aqueous extract of P. auritum (PA, single administration) were investigated in the fictive ejaculation, and copulatory behavior paradigms in sexually sluggish male rats. WAY 100635 (antagonist of 5-HT1A receptors), atosiban (antagonist of oxytocinergic receptors), L-NAME (inhibitor of the nitric oxide synthase) and baclofen (antagonist of GABAB receptors) were used as pre-treatments in order to investigate the role of different neurotransmitter systems in PA actions. Chemical profile of PA was determined by Gases Chromatography and Ultra Performance Chromatography-Electrospray Ionization-Masses Spectrometry (UPLC-ESI-MS). RESULTS: In males with retarded ejaculation, PA stimulated ejaculatory behavior and recovered electromyographic activity of pelvic musculature participating in seminal emission and ejaculation. All pre-treatments blocked stimulating effects of PA on the fictive ejaculation; additionally WAY 100635 interfered with PA actions on ejaculatory behavior. Safrol, apigenin dimethylether, myristicin, vaccihein A, sakuranin and sakuranetin flavonoids, were main constituents of PA, with possible participation in its pro-sexual effects. CONCLUSIONS: Pro-sexual effects of P. auritum elicited at level of ejaculation were mediated by several neurotransmitter systems, among which serotonin and its 5-HT1A receptors play an important role. Present findings support P. auritum reputation as an aphrodisiac, with potential use in delayed ejaculation disorder.

Antidepressant effects of acupoint stimulation and fluoxetine by increasing dendritic arborization and spine density in CA1 hippocampal neurons of socially isolated rats.

Given the importance of depression and the adverse effects of conventional treatment, it is necessary to seek complementary therapies. In a rat model of depression, this study aimed to assess the behavioral and morphological effects of embedding absorbable thread in acupoints (acu-catgut), and compare the results to those of fluoxetine treatment and the corresponding control groups. Therefore, depressive-like behavior was evaluated with the forced swimming test, and dendritic morphology (in the CA1 hippocampal region) with the Golgi-Cox technique and Sholl analysis. After weaning, male Sprague-Dawley rats were housed in social isolation for 8 weeks to induce depressive-like behavior. They were then given a 21-day treatment by stimulating acupoints with acu-catgut (AC) or fluoxetine (FX) (2 mg/kg). Rats were divided into six groups: Control (socially housed), social isolation (SI), SI + AC, SI + Sham (sham embedding of thread), SI + FX and SI + VH (vehicle). Compared to fluoxetine, acu-catgut treatment was more effective in reversing depressive-like behavior elicited by SI. The SI-induced reduction in dendritic length and spine density in hippocampal CA1 pyramidal neurons was attenuated after prolonged treatment with acu-catgut or fluoxetine. Hence, both treatments proved capable of reversing depressive-like alterations caused by SI, likely due to dendritic remodeling in the hippocampus.