Yohimbine

The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug.

BackgroundReserpine is an effective antihypertensive drug, but its role in routine practice has declined such that it is rarely used. This is largely based on the assumption that reserpine causes depression. This assumption was a foundation for the original monoamine hypothesis of depression. However, there remains conflicting evidence as to whether reserpine causes depression, and no systematic review of available evidence.AimsWe systematically reviewed evidence on effects of reserpine on depressive and related symptoms (e.g. anxiety, suicidal ideation).MethodElectronic searches of MEDLINE, Embase and PsycINFO were conducted to identify studies up to 14 February 2021. Studies of any methodological design involving reserpine-treated and reserpine-untreated conditions, in any adult human population, were included and a narrative synthesis of findings was undertaken. Risk of bias (RoB) was examined using ROBINS-I.ResultsOf the 35 studies meeting inclusion criteria, 9 were randomised controlled trials. Eleven studies reported some depressogenic effects, 13 reported no effect and 11 reported putative antidepressant effects. Studies identifying depressive effects were more likely to examine people without psychiatric disorders at baseline, while studies identifying a potential antidepressant effect tended to treat fewer participants for shorter durations, at higher doses. Around one-third of studies conducted in people with psychiatric disorders showed beneficial effects on depression symptoms. 30/35 studies were at high RoB.ConclusionsAssociations between reserpine and depression are inconsistent and limited by a lack of high-quality evidence. Due to reserpine's apparently complex effects, we urge nuance rather than simplicity surrounding the monoamine hypothesis of depression.

Mental disorders have a poor clinical prognosis and account for approximately 8% of the global burden of disease. Some examples of mental disorders are anxiety and depression. Conventional antidepressants have limited efficacy in patients because their pharmacological effects wear off, and side effects increase with prolonged use. It is claimed that herbal medicine's antioxidant capacity helps regulate people's mood and provide a more substantial pharmacological effect. With this background, the purpose of this study is to investigate the effect of rutin on reserpine-induced anxiety and depression in rats. The animals were divided into groups of six rats each: normal control (water), a depression model, a rutin-treated rat model, and an amitriptyline-treated rat model. According to the results, 14 days of treatment with rutin, once daily, showed a modest antidepressant effect. This effect was mediated by increased serotonin, norepinephrine, and dopamine levels in cortical and hippocampal regions. The antioxidant and vasodilator properties of rutin may contribute to its antidepressant properties. According to this study, rutin has shown antidepressant effects by reducing antioxidant activity and acetylcholinesterase.

Fibromyalgia (FM) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, psychological disturbances, and sleep issues. Honokiol (HNK) is a bioactive compound known for its medicinal properties. This study evaluated HNK's effectiveness in alleviating pain, depression, and anxiety in a reserpine-induced FM rat model. Thirty male rats were divided into three groups: control, RES (FM-induced), and RES + HNK. HNK was supplemented to RES + HNK in a dose of 8 mg/kg for 21 days. Behavioral assessments included the open field, elevated plus maze, and forced swim tests, while pain was evaluated using treadmill endurance, tail flick latency, paintbrush, and rotarod tests. Brain homogenates were analyzed for neurotransmitters, antioxidants, pro-inflammatory cytokines, and gene expressions. Histopathological evaluation of spinal cords assessed markers of inflammation and apoptosis. Results showed that HNK administration improved behavior and reduced pain. This was linked to reduced levels of malondialdehyde, tumor necrosis factor-α, and prostaglandin E2, alongside increased superoxide dismutase and interleukin-10. Additionally, HNK downregulated the expression of calcitonin gene-related peptide and the JAK/STAT3 gene. These findings suggest that HNK alleviates FM symptoms through its antioxidant, anti-inflammatory, neuroprotective, and anti-apoptotic properties, indicating its potential as a therapeutic agent for FM.