Neuropsychopharmacological Induction of (Lucid) Dreams: A Narrative Review.

Lucid dreaming (LD) is a physiological state of consciousness that occurs when dreamers become aware that they are dreaming, and may also control the oneiric content. In the general population, LD is spontaneously rare; thus, there is great interest in its induction. Here, we aim to review the literature on neuropsychopharmacological induction of LD. First, we describe the circadian and homeostatic processes of sleep regulation and the mechanisms that control REM sleep with a focus on neurotransmission systems. We then discuss the neurophysiology and phenomenology of LD to understand the main cortical oscillations and brain areas involved in the emergence of lucidity during REM sleep. Finally, we review possible exogenous substances-including natural plants and artificial drugs-that increase metacognition, REM sleep, and/or dream recall, thus with the potential to induce LD. We found that the main candidates are substances that increase cholinergic and/or dopaminergic transmission, such as galantamine. However, the main limitation of this technique is the complexity of these neurotransmitter systems, which challenges interpreting results in a simple way. We conclude that, despite these promising substances, more research is necessary to find a reliable way to pharmacologically induce LD.

Green coffee extract attenuates Parkinson's-related behaviors in animal models.

Epidemiological studies have shown an inverse association between coffee consumption and the development of Parkinson's disease (PD). The effects of the oral treatment with green (non-roasted) coffee extracts (CE, 100 or 400 mg/kg) and caffeine (31.2 mg/kg) were evaluated on catalepsy induced by haloperidol in mice, and unilateral 6-OHDA lesion of medial forebrain bundle (MFB) or striatum in rats. Also, the in vitro antioxidant activity and the monoamine levels in the striatum were investigated. CE presented a mild antioxidant activity in vitro and its administration decreased the catalepsy index. CE at the dose of 400 mg/kg induced ipsilateral rotations 14 days after lesion; however, chronic 30-day CE and caffeine treatments did not interfere with the animals' rotation after apomorphine or methamphetamine challenges in animals with MFB lesion, nor on monoamines levels. Furthermore, CE and caffeine were effective in inhibiting the asymmetry between ipsilateral and contralateral rotations induced by methamphetamine and apomorphine in animals with lesion in the striatum but did not avoid the monoamines depletion. These results indicate that CE components indirectly modulate dopaminergic transmission, suggesting a pro-dopaminergic action of CE, and further investigation must be conducted to elucidate the mechanisms of action and the possible neuroprotective role in PD.

Effect of Experimental Ischemic Stroke and PGE2 EP1 Selective Antagonism in Alzheimer's Disease Mouse Models.

BACKGROUND: Neuroinflammation has been recognized as an important factor in the pathogenesis of Alzheimer's disease (AD). One of the most recognized pathways in mediating neuroinflammation is the prostaglandin E2-EP1 receptor pathway. OBJECTIVE: Here, we examined the efficacy of the selective EP1 antagonist ONO-8713 in limiting amyloid-ß (Aß), lesion volumes, and behavioral indexes in AD mouse models after ischemic stroke. METHODS: Transgenic APP/PS1, 3xTgAD, and wildtype (WT) mice were subjected to permanent distal middle cerebral artery occlusion (pdMCAO) and sham surgeries. Functional outcomes, memory, anatomical outcomes, and Aß concentrations were assessed 14 days after surgery. RESULTS: pdMCAO resulted in significant deterioration in functional and anatomical outcomes in the transgenic mice compared with the WT mice. No relevant differences were observed in the behavioral tests when comparing the ONO-8713 and vehicle-treated groups. Significantly lower cavitation (p = 0.0373) and percent tissue loss (p = 0.0247) were observed in APP/PS1 + ONO-8713 mice compared with the WT + ONO-8713 mice. However, the percent tissue injury was significantly higher in APP/PS1 + ONO-8713 mice compared with the WT + ONO-8713 group (p = 0.0373). Percent tissue loss was also significantly lower in the 3xTgAD + ONO-8713 mice than in the WT + ONO-8713 mice (p = 0.0185). ONO-8713 treatment also attenuated cortical microgliosis in APP/PS1 mice as compared with the vehicle (p = 0.0079); however, no differences were observed in astrogliosis across the groups. Finally, APP/PS1 mice presented with characteristic Aß load in the cortex while 3xTgAD mice exhibited very low Aß levels. CONCLUSION: In conclusion, under the experimental conditions, EP1 receptor antagonist ONO-8713 showed modest benefits in anatomical outcomes after stroke, mainly in APP/PS1 mice.

Comparison of the chemical composition and biological effects of the roots, branches and leaves of Heteropterys tomentosa A. Juss.

ETHNOPHARMACOLOGICAL RELEVANCE: HETEROPTERYS TOMENTOSA: A. Juss (Malpighiaceae), commonly mistaken as Heteropterys aphrodisiaca, is chronically used by the Brazilian population to improve general health due to its claimed protective effects against a wide range of medical conditions. AIM OF THE STUDY: This study in rodents aimed to verify the adaptogenic potential of the hydroalcoholic extracts of the roots (the most commonly used portion), branches and leaves of the plant. MATERIALS AND METHODS: The phytochemical constitution of the extracts was analyzed through thin-layer chromatography and high-performance liquid chromatography. Restriction- and cold-induced stress in rats treated for 14 days with 100 or 300 mg/kg of the extracts were used to evaluate parameters such as ulceration, adrenals, thymus and spleen weights, as well as ACTH and corticosterone plasmatic levels. The stress response also was evaluated in mice by self-analgesia induced by restraint stress, after 7 days of treatment at doses of 100 and 300 mg/kg. The learning and memory of aged rats treated with extracts of root or branches at the dose of 50 mg/kg for 80 days were evaluated in the elevated T-maze test. RESULTS: The chemical constituents of the three parts of the plant were relatively similar in the presence of saponins, hydrolysable tannins, flavonoids, polyphenols and triterpenes. None of the three extracts were capable of protecting the stomach from ulcerations in rats submitted to cold restraint stress or protecting from alterations in adrenal or spleen weight (p>0.05). Furthermore, the extracts did not inhibit increases in plasma levels of corticosterone and adrenocorticotropic hormone. Moreover, the extracts did not inhibit self-analgesia induced by restraint stress in mice and did not improve the performance of aged rats in the T-maze test (p>0.05). CONCLUSION: The tests employed in this study did not show evidence of adaptogenic activity in the three extracts of Heteropterys tomentosa.

Tonic, fortifier and aphrodisiac: adaptogens in the Brazilian folk medicine

In Brazil, many plants are used as tonic, fortifier, aphrodisiac, anti-stress, among other uses that are similar to the indications of an adaptogen. In general, such plants are used unspecifically, in situations of stress and fatigue, in the recovery after a previous pathological or debilitating state, or simply aiming at the maintenance of a healthy state. This article discusses the popular terms employed in the Brazilian folk medicine for the plants with this profile, their particularities and limitations. The article also discusses the possible mechanisms of action of an adaptogen and compares the main Brazilian plants used for that purpose: guarana (Paullinia cupana Kunth, family Sapindaceae), muirapuama (Ptychopetalum olacoides Benth., Olacaceae), catuaba (Anemopaegma arvense (Vell.) Stellfeld & J.F. Souza, Bignoniaceae, and Trichilia catigua A. Juss., Meliaceae), nó-decachorro (Heteropterys aphrodisiaca O. Mach, Malpighiaceae), damiana (Turnera diffusa Willd. ex Schult., Turneraceae) and pfaffia or Brazilian ginseng (Pfaffia sp, Amaranthaceae).

Effects of a hydroalcoholic extract of Turnera diffusa Willd. ex Schult., Turneraceae, in tests for adaptogenic activity

The objective of the present study was to assess whether Turnera diffusa Willd. ex Schult., Turneraceae, (TD), plant known in popular medicine as tonic and aphrodisiac, has other effects that are characteristic of an adaptogen substance, such as improvement of the memory and reduction of the damage caused by stress. We carried out an initial screening to detect a possible toxicity of the plant. In that phase of the study we used tests of observational screening; evaluation of acute toxicity; measurement of motor activity and motor coordination, and sleeping time induced by pentobarbital, and observed that the extract presented low toxicity and no stimulant or depressant effect on the animals. We then performed specific tests for the evaluation of an adaptogen effect. TD did not protect the stomach of the animals from the formation of ulcers, neither did it alter the plasmatic levels of adrenocorticotropic hormone (ACTH) and corticosterone of the animals submitted to immobilization and cold. As regards the evaluation of memory in passive avoidance, TD did not inhibit scopolamine-induced amnesia. Additionally, the hydroalcoholic extract presented low antioxidant activity in vitro. In the models used, TD produced no changes in relation to a possible adaptogen effect.

Antinociceptive peripheral effect of Achillea millefolium L. and Artemisia vulgaris L.: both plants known popularly by brand names of analgesic drugs.

The hydroalcohol extracts of Achillea millefolium L. (AM) and Artemisia vulgaris L. (AV), both belonging to the Asteraceae family, were evaluated by the hot plate, writhing, formalin and intestinal transit tests in an attempt to confirm their folk use as analgesic, antiinflammatory and antispasmodic agents. AM 500 and 1000 mg/kg significantly inhibited abdominal contortions by 65% and 23%, respectively, whereas AV 500 and 1000 mg/kg inhibited them by 48% and 59%, respectively. None of the extracts produced differences in the intestinal transit in mice, nor in the response time in the hot plate or in the immediate or late responses in the formalin test. In HPLC/DAD analyses 'fingerprint', monitored at 360 and 270 nm, both hydroalcohol extracts showed the same flavonoid glycoside as a principal constituent, which was identified as rutin. A high content of caffeic acid derivatives were also found in both extracts. The main differences were observed at 240 nm: AM had a higher content of rutin, while in AV the hydroxybenzoic acid derivative was the major component.

Preliminary investigation of the central nervous system effects of 'Tira-capeta' (Removing the Devil), a cigarette used by some Quilombolas living in Pantanal Wetlands of Brazil.

During an ethnopharmacological survey carried out among some Quilombolas living in Brazil, 48 plants with possible central nervous system (CNS) action were cited. A mixture of nine plants, known as 'Tira-capeta' (Removing the Devil) cigarette, has been utilized for years as a tonic for the brain. The effects observed after consuming this cigarette are: dizziness, lightness sensation, humor changes, yawns, heavy eyes, hunger, sleep and relaxation. This study aimed to verify the effects of a hydroalcohol extract of 'Tira-capeta' cigarette (ETC), as well as to evaluate the phytochemical profile. The phytochemical screening carried out through characterization reactions, thin layer chromatography and high efficiency liquid chromatography indicated the presence of tannins, phenolic acids, flavonoids, saponins and alkaloids; tannins and phenolic acids being the principal constituents. The pharmacological tests showed that ETC induced a biphasic effect, with intense initial stimulation of the CNS, followed by a general depressor state; decreased the latency for sleeping and increased the total sleeping time (50, 100 and 500 mg/kg), without causing prejudice in motor coordination (doses up to 200 mg/kg); induced catalepsy in mice, verified 10 and 50 min after drug administration (500 mg/kg). Also, no anxiolytic or anxiogenic effects were verified in rats submitted to the elevated plus-maze.

Treatment of drug dependence with Brazilian herbal medicines / Tratamento da dependência de drogas com plantas medicinais brasileiras

The topic "Herbal Medicines in the Treatment of Addictions" in a country must be preceded by answers to four questions: 1. Does the country in question possess a biodiversity rich enough to allow the discovery of useful medicines? 2. Do local people have tradition and culture to look for and use resources from Nature to alleviate and cure diseases, including drug dependence? 3. Is drug dependence (or addiction) present in the country in question? 4. Do people of that country recognize and diagnose such problem as a serious one? Alcohol is, by far, the most serious health problem when drug abuse is considered, reaching all of Brazilian society, including the Indians. On the contrary, other drugs may be considered as minor problems and they are not the main focus of this manuscript. The people living in Brazilian hinterland don’t have access to public health systems. Consequently, these people seek assistance from "curandeiros" and "raizeiros"; the Indians are assisted by the shaman. These "folk doctors" do not know the academic medicine and therapeutics, and resort to the local plants to treat different ailments of their patients. Furthermore, alcohol abuse and dependence are not recognized by them, according to the rules and criteria of academic medicine. We have conducted a survey in many Brazilian books, Thesis concerning phytotherapy, and several databank. The results of such searches were very disappointing. No published papers from Brazilian authors concerning the use of plants for the treatment of addictions were found in the databases and there were only three very short notes in the masterly book written by Shultes and Raffauf (1990). From the Brazilian books on folk medicine employing medicinal plants, ten mentions were disclosed: most of them dealing with treatment of alcohol problems and two to counteract "Ayahuasca" dependence.

O tema "Plantas medicinais no tratamento de dependência" em um país deve ser precedido pela resposta a quatro questões: 1. O país em questão possui biodiversidade suficiente para permitir a descoberta de remédios naturais úteis? 2. Seus habitantes possuem tradição e cultura de procurar e utilizar recursos da natureza para aliviar e curar doenças, incluindo dependência de drogas? 3. O problema de dependência de drogas está presente no país em questão? 4. Seus habitantes reconhecem e diagnosticam a dependência de drogas como um sério problema? O álcool é, de longe, o mais sério problema de saúde quando o assunto abuso de drogas é considerado, atingindo toda a sociedade brasileira, incluindo os índios. Ao contrário, outras drogas podem ser consideradas como problemas menores e não são o foco principal deste artigo. As pessoas vivendo nas terras brasileiras mais isoladas não têm acesso ao sistema público de saúde. Conseqüentemente, estas pessoas procuram tratamento com curandeiros e raizeiros; ou, no caso dos indígenas, com os shamans. Estes doutores populares não conhecem a medicina e terapêutica acadêmicas e recorrem a plantas locais para tratar as diferentes patologias que acometem seus pacientes. Entretanto, o abuso e dependência de álcool não são vistos por eles como problemas de saúde segundo as regras e critérios da medicina acadêmica. Um levantamento foi feito em diversos livros brasileiros, teses sobre fitoterapia e alguns bancos de dados. Os resultados de tal pesquisa foram frustrantes. Não foram encontrados artigos de autores brasileiros sobre o uso de plantas para o tratamento de dependência de drogas nos bancos de dados consultados e apenas três notas muito curtas em um livro clássico escrito por Shultes e Raffauf (1990). Dos livros brasileiros sobre o uso popular de plantas medicinais, foram obtidas dez menções: a maioria delas sobre o tratamento de problemas relatados ao álcool e duas delas a respeito do tratamento da dependência de "Ayahuasca".

Effects of androgen manipulation on alpha1-adrenoceptor subtypes in the rat seminal vesicle.

This study analyses possible changes during surgical and chemical castration in the expression and pharmacological characteristics of alpha1-adrenoceptor in adult rat seminal vesicle. Ribonuclease protection assays indicated that alpha1a--was the predominant mRNA, while alpha1b-and alpha1d-adrenoceptor transcripts were detected in lower abundance in this tissue. alpha1a-adrenoceptor mRNA expression presented a complex dependency on androgens, while alpha1b- and alpha1d-adrenoceptor transcripts were both upregulated with surgical and chemical castration, suggesting a negative modulation by androgens. Testosterone treatment reversed the effects caused by surgical castration. Functional studies confirmed the involvement of alpha1A- and alpha1B-adrenoceptor in the seminal vesicle contractile responses, and suggested that alpha1B-induced contractile response was upregulated after castration. Taken together, the results suggest that alpha1-adrenoceptor expression in seminal vesicle is differentially regulated by the androgen status of the rat.

Alpha1-adrenoceptor subtypes in rat epididymis and the effects of sexual maturation.

We have characterized the expression of alpha1-adrenoceptor in epididymis from rats in different stages of sexual maturation: 40 (immature), 60 (young adult), and 120 (adult) days of age. Plasma testosterone levels were low in the immature animals but increased significantly in the 60- and 120-day-old animals. These changes were followed by a progressive increase in rat body weight and in caput and cauda epididymis relative weight. Reverse transcription polymerase chain reaction assay indicated that alpha1a-, alpha1b-, and alpha1d-adrenoceptor transcripts were present in both caput and cauda epididymis from adult rats. Ribonuclease protection assays further indicated that the expression of these alpha1-adrenoceptor transcripts differed with age and epididymal region analyzed. Prazosin (nonselective alpha1 antagonist), 5-methyl urapidil (alpha1A-selective), and BMY 7378 (alpha1D-selective) displaced [3H]prazosin binding curves in caput and cauda epididymis from 40- and 120-day-old rats. The potency order for these antagonists, as calculated from the negative logarithm of the inhibition constant (pK(i)) values for the high-affinity sites, indicated a predominant population of alpha1A-adrenoceptor subtype in caput and cauda epididymis from adult animals. Differences in pK(i) values in caput and cauda epididymis from immature and adult animals also suggested that the relative amount of alpha1-adrenoceptors, at the protein level, is modulated by sexual maturation. Taken together, the changes in alpha1-adrenoceptor expression during sexual maturation may suggest specific roles for these receptors in epididymal function.