Doses Of Buspirone Research Articles

Role of 5-HT1A Receptor on Fluvoxamine induced Gastrointestinal Mucosa Protection and Healing in Animal with Stress-Induced Gastric Ulcer

One factor that could contribute to the developing of gastric ulcer is stress. Fluvoxamine, an SSRI antidepressant showed protective effects to ulcers when administered before stress induction. In opposite, administration of fluvoxamine after stress induction delayed the mucosa healing. This study aimed to investigate the effects of pre-treatment and post-treatment of buspirone a 5-HT1A receptor partial agonist in the inhibition of gastric mucosal protection and healing by fluvoxamine in animals with stress-induced gastric ulcers. This study used ddY, male mice, weighed 25-30grams, which divided into two groups, pre-treatment and post-treatment groups. Each group consisted of subgroups that were administered low doses of buspirone (0.1mg/Kg and 0.3mg/Kg) and high doses of buspirone (10.0mg/Kg and 30.0mg/Kg). In the pre-treatment group, buspirone was administered intraperitoneally at 60 minutes before and continued with oral fluvoxamine 100mg/Kg administration at 30 minutes before stress induction. In the post-treatment group, buspirone was administered intraperitoneally followed fluvoxamine orally 30 minutes after stress induction done. The stress model used is water immersion restrain stress for 6 hours. In the pre-treatment group, the combination of high dose, but not low dose buspirone significantly inhibit the protection effects of fluvoxamine on stress-induced gastric ulcers. In addition, in the post-treatment group, the combination of low dose buspirone and fluvoxamine strengthen the delays of mucosal healing by fluvoxamine in mice with stress-induced gastric ulcers. Fluvoxamine protects and heals gastric mucosa from stress-induced gastric ulcer through the activation of 5HT1A receptor.

Co-treatment with low doses of buspirone prevents rewarding effects of methylphenidate and upregulates expression of 5-HT1A receptor mRNA in the nucleus accumbens

Accumulating studies consistently show that methylphenidate (MPD), the first line drug for treating Attention-Deficit Hyperactivity Disorder (ADHD), is abused by patients to whom the drug is prescribed. Like other psychostimulants, only low doses of MPD improve cognitive performance while higher doses impair it. Preventing the use of high doses of MPD is important for retaining its therapeutic efficacy. Previously, it has been shown that performance in Morris water maze test is improved in rats treated, orally, with MPD in doses of 2.5 mg/kg; but higher doses (5 mg/kg) impair it. The present study is designed to monitor rewarding effects of 2.5 mg/kg MPD in conditioned place preference (CPP) paradigm and its potential inhibition in buspirone co-treated animals. Our results show that rewarding effects of MPD in CPP paradigm are prevented in rats co-treated with buspirone in doses of 0.1 and 0.3 mg/kg. Animals treated with MPD exhibit a downregulation of 5-HT1A receptor mRNA in the nucleus accumbens which is also prevented in rats co-treated with 0.1 and 0.3 mg/kg but not 1.0 and 2.0 mg/kg buspirone. Administration of buspirone in these doses is not rewarding in CPP test and upregulates 5-HT1A receptor mRNA in the nucleus accumbens. The findings suggest that co-use of low doses of buspirone can prevent rewarding effects of MPD to help retain its therapeutic efficacy

Amount of < 1Hz deep sleep correlates with melatonin dose in military veterans with PTSD

Military veterans with posttraumatic stress disorder often complain of non-restful sleep, which further exacerbates their symptoms. Our previous study showed a deficit in Lo Deep sleep, or slow oscillations, in the PTSD population compared to healthy control sleepers. Because Lo Deep sleep is likely a stage when the brain eliminates protein debris, it is critical to find the cause and effective therapeutics to reverse Lo Deep deficiency. The current study aims to replicate and extend this finding by examining several physiological and medication factors that may be responsible for the Lo Deep deficiency. We recorded overnight sleep electroencephalogram (EEG) via a 2-channel headband device on 69 veterans in a residential treatment facility. Dried urine samples were collected at 4 time points during one day to measure melatonin, cortisol, norepinephrine and other factors. EEG data were transformed into frequency power and submitted to an automated sleep scoring algorithm. The scoring corresponds to clear spectral patterns in the overnight spectrogram but does not align exactly with traditional visual scoring stages. As expected, veterans showed decreased Lo Deep (activity < 1 Hz) and more Hi Deep sleep (1–3 Hz activity) than healthy controls, replicating our previous study. Multiple linear regressions showed that melatonin dose and morning urine melatonin correlated with more Lo Deep sleep. Buspirone dose also correlated with more Lo Deep, but only 6 subjects were taking buspirone. Also replicating the findings from our last study were independent reductions of REM sleep with prazosin and sertraline. Other findings included decreased Lo and increased Hi Deep sleep with higher caffeine dose, and less Hi Deep percentage with higher testosterone. Finally, evening cortisol levels correlated with a higher percentage of Wake after sleep onset. These results confirm Lo Deep deficiency in this PTSD population and suggests melatonin as a possible therapeutic to reverse Lo Deep deficiency. This is a critical first step to establishing a systematic sleep assessment and treatment program in this and potentially other populations to prevent future brain pathology.

An anxiolytic drug buspirone ameliorates hyperglycemia and endothelial dysfunction in type 2 diabetic rat model

Abstract Objectives Type 2 diabetes is a common metabolic disease and anxiety disorders are very common among diabetics. Buspirone is used in the treatment of anxiety, also having blood glucose-lowering effects. The aim of the study was to investigate the effects of buspirone on the glucose and lipid metabolism as well as vascular function in type 2 diabetic rats. Methods A type 2-diabetic model was induced through a high-fat diet for eight weeks followed by the administration of low-dose streptozotocin (35 mg/kg, intraperitoneal) in rats. Buspirone was given at two different doses (1.5 mg/kg/d and 5 mg/kg/d) and combined with metformin (300 mg/kg/d). The fasting glucose and insulin levels, lipid profile were analyzed, and vascular response measured from the thoracic aorta was also evaluated. Results Both doses of buspirone caused a significant improvement in fasting blood glucose levels. In particular, the buspirone treatment, combined with metformin, improved endothelial dysfunction and was found to be correlated with decreased nitrate/nitrite levels. Conclusions Buspirone may be effective in the treatment of type 2 diabetes, either alone or in combination with other treatments, particularly in terms of endothelial dysfunction, inflammation and impaired blood glucose, and insulin levels.

Comparison of the Efficacy of Buspirone and Placebo in Childhood Functional Abdominal Pain: A Randomized Clinical Trial.

Pharmacological interventions have not been successful in the treatment of childhood functional abdominal pain (FAP) hitherto. Buspirone is suggested to be efficacious in some of the abdominal pain-related functional gastrointestinal disorders based on evidences from the studies on adults. We aim to investigate the efficacy of buspirone on childhood FAP. This randomized clinical trial was conducted on 117 patients with childhood FAP aged 6-18 years. We randomly assigned patients to receive buspirone or placebo for 4 weeks, with the adjusted dosage for age. Participants completed the questionnaires assessing pain, depression, anxiety, somatization, and sleep disturbances at baseline, at the end of the 4-week therapy (first follow-up), and at 8 weeks after medication discontinuation (second follow-up). The primary outcome was treatment response rate, defined as reduced pain score of ≥2 or reporting no pain at the follow-up assessments. Ninety-five patients completed the 4-week therapy (48 and 47 in buspirone and placebo groups, respectively). Both buspirone and placebo reduced pain after 4 weeks of treatment, and these effects were persistent 8 weeks after medication discontinuation (P < 0.001 for both groups at weeks 4 and 12). Treatment response rates for buspirone and placebo were 58.3% and 59.6% at week 4 (P = 0.902) and 68.1% and 71.1% at week 12 (P = 0.753), respectively. Buspirone effectively improves pain and associated psychological symptoms including depressive symptoms, anxiety, somatization, and sleep disturbances in childhood FAP but has no superiority over placebo. Further studies, with the higher doses of buspirone and longer follow-ups are recommended.

Evaluation of anti-anxiety activity of Mucuna pruriens

Mucuna pruriens, also known as Velvet Bean, Mucuna pruriens has been used for centuries by Ayurvedic herbalists for overall wellness. Mucuna pruriens provides support for brain function, muscle health and libido. Mucuna pruriens has also been shown to have diuretic effects. It increases tissue resiliency and improves coordination. Mucuna can also increase testosterone levels, which in turn can lead to increased muscle mass and strength. It also supports the nervous and reproductive systems in the body. anti-oxidant activity of M. pruriens has been also demonstrated in vitro by its ability to scavenge DPPH radicals and reactive oxygen species. This is an excellent natural source of L-dopa and 5-hydroxy tryptophan (5-HT) Present study was designed to evaluate the anti-anxiety activity of Mucuna pruriens extract in Swiss albino mice. Three doses of Mucuna pruriens (100, 200,400 mg/kg, p.o.) and standard dose of Buspirone (5 mg/kg, i.p.) were used for evaluation of the anti-anxiety activity. The elevated plus maze (EPM) was used to take as a measure of antianxiety effect. Mucuna pruriens at the doses of 200 mg/kg and 400 mg/kg significantly reduced the time spent and no. of entries in closed arm, increased the time spent and entries into open arm in elevated plus maze (p&lt;0.05) as compared to control group. These results indicate that MP may be possesses antianxiety property. Keywords: Anxiety, Elevated plus maze, Mucuna pruriens, Buspirone, Swiss Albino Mice.

The Effects of Morphine, Baclofen, and Buspirone Alone and in Combination on Schedule-Controlled Responding and Hot Plate Antinociception in Rats.

Better therapeutic options are needed for pain. Baclofen, buspirone, and morphine are characterized as having analgesic properties. However, little is known about potential interactions between analgesic effects of these drugs when combined. Furthermore, it is not known if the magnitude of these potential interactions will be similar for all drug effects. Thus, we tested the effects of these drugs alone and in combination for their capacity to produce thermal antinociception and to decrease food-maintained responding. Four male and four female Sprague-Dawley rats responded for food under a fixed-ratio 10 schedule; afterward they were immediately placed on a 52°C hot plate. Morphine, baclofen, and buspirone were examined alone and in 1:1 combinations, based upon ED50 values. Morphine and baclofen effects were evaluated with the opioid antagonist naltrexone and the GABAB antagonist (3-Aminopropyl)(diethoxymethyl)phosphinic acid (CGP35348), respectively. Morphine, baclofen, and buspirone dose dependently decreased operant responding, with the calculated ED50 values being 7.09, 3.42, and 0.57 mg/kg, respectively. The respective antinociception ED50 values were 16.15, 8.75, and 2.20 mg/kg. Analysis of 1:1 combinations showed the effects of morphine plus baclofen to decrease schedule-controlled responding and to produce thermal antinociception were synergistic. Effects of morphine plus buspirone and baclofen plus buspirone to decrease schedule-controlled responding were additive. Effects of the two combinations to produce thermal antinociception were synergistic. Naltrexone and CGP35348 antagonized the effects of morphine and baclofen, respectively. Synergistic antinociceptive effects, in conjunction with additive effects on food-maintained responding, highlight the therapeutic utility of opioid and non-opioid drug combinations.

Effect of buspirone on blood glucose levels in rats

Background: Buspirone is commonly used as an anti-anxiety drug. There is controversy over the dysglycemic effects of buspirone in various clinical and animal studies. Aims and Objectives: This study aims to evaluate the effect of buspirone on blood sugar level in rats at three different doses. Materials and Methods: Rats were treated with three doses of buspirone orally, namely, 3 mg/kg, 5 mg/kg, and 10 mg/kg and control group received distilled water orally for 14 days. Blood was collected by tail prick method at 0 h (fasting), at ½ h, 1 h, 1½ h, 2 h, and 4 h after drug administration on day 1. On days 7 and 14, the blood glucose levels were estimated at baseline (0 h) and at 1 h after the drug administration. Blood glucose levels were estimated using the glucometer. Results: On day 1, mean blood glucose values were found to be significantly (P < 0.001) low in control group and in buspirone 3 mg/kg and 5 mg/kg groups at various time intervals as compared to baseline value at 0 h in respective group. In buspirone 10 mg/kg group, mean blood glucose levels at all-time intervals were found to be significantly high (P < 0.01) as compared to baseline value at 0 h. On days 7 and 14, a significant increase in the blood glucose level was observed immediately within 30 min of drug administration and reach maximum value at the end of 1 h only in buspirone 10 mg/kg group. This rise in blood glucose level was not seen in groups receiving buspirone 3 mg/kg and 5 mg/kg. Conclusion: Buspirone 3 mg/kg and 5 mg/kg does not have any effect on blood glucose levels, while in a high dose of 10 mg/kg causes a significant transient increase in the blood glucose level.

Dose related effects of buspirone on pain, learning / memory and food intake

The present study concerned extending the therapeutic use of buspirone for treating pain and improving cognition. Effects of single and repeated administration of buspirone were therefore monitored on pain threshold in the hot plate test and on spatial memory in the water maze test in rats. Effects on cumulative food intake were also monitored. The drug was administered intraperitoneally in doses of 0.1, 0.3, 1.0 and 2.0 mg/kg. We found that single and repeated administration of buspirone in doses of 0.1 mg/kg decreased pain threshold in the hot plate test, while doses of 1.0 and 2.0 mg/kg increased it. Effects of single and repeated administration were not different. A dose of 0.3 mg/kg had no effect. Food intake increased following single as well as repeated administration of 0.1 mg/kg buspirone; higher doses had no effect. Low doses (0.1 and 0.3 mg/kg) improved acquisition and retention of memory in the water maze test, while memory extinction was reduced. Higher doses had either no effect (1.0 mg/kg) or impaired (2.0 mg/kg) performance in this test. The results suggest potential therapeutic use of selected doses of buspirone as an analgesic and nootropic drug.

Effect of Buspirone on Fetuses of the Pregnant Rats

Aim of the work: the purpose of this study was to detect effect of buspirone hydrochloride (Buspar) on the structure of cerebellum cortex of the fetuses of the pregnant rats. Material and methods: buspirone hydrochloride tablets are an antianxiety. Buspirone hydrochloride (buspar) tablets were obtained from SmithKline Beecham-Haram-Giza- Egypt. Thirty pregnant female rats were randomly categorized into three groups (Ten pregnant female rats in each group). Group I (control group) pregnant rats were administered oral doses of distilled water, group II: in this group pregnant rats were treated with buspirone hydrochloride, they were administered oral doses of drug in the distilled water equivalent to 0.27 mg/100g. body weight/day respectively for 15 days from the 6th day to the 20th day of gestation. , group III: pregnant rats were treated with to oral doses of buspirone hydrochloride in the distilled water equivalent to 0.41 mg/100g. body weight/day respectively for 15 days from the 6th day to the 20th day of gestation. Pregnat rats of all groups were sacrificed on the 20th day of gestation and their fetuses were obtained for the histopathological and histochemical studies. Results: treatment of pregnant rats with buspirone hydrochloride (buspar) showed many dystrophic changes in brain of their fetuses; these changes were more obvious in case of the toxic dose of buspirone which resulted in some sorts of neurotoxic structural changes in the cerebellum of fetuses of pregnant rats as evident by deformity in the cerebellar layers and degeneration of Purkinje cells. Conclusions: buspirone hydrochloride (buspar) has many adverse effects on the fetal cerebellum tissue.

Concurrent Serotonin Syndrome and Hyponatremia: A Case Report and Review

Introduction: These days, selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed and used antidepressants. Serotonin syndrome is a potentially fatal complication with hyper-serotonergic situation. Its symptoms result from over activation of the central and peripheral receptors caused by high serotonin levels. The use of SSRIs is associated with the frequency of syndrome. Hyponatremia is one of the side effects of SSRIs, especially in elderly patients. The mechanism by which SSRIs cause hyponatremia is thought to be secondary to the development of the syndrome of inappropriate antidiuretic hormone (SIADH). Patients with hyponatremia secondary to SIADH have been reported with fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram. There are very few reports about the concurrent incidence of serotonin syndrome and hyponatremia. Case Presentation: The patient was a 66-year-old woman with rheumatoid arthritis. She was treated with a fixed dose of fluoxetine and buspirone added with the amount of 15 mg per day. The patient was hospitalized 8 weeks with symptoms of confusion, lack of insight into time and space, inability to stand and walk, continuous involuntary tremor, uncoordinated and uncontrolled movements of arms and legs, hyperreflexia, and mydriasis. She also showed severe hyponatremia in the experiments. She was admitted to an academic general hospital in Iran on 2014. Based on the clinical findings, taking buspirone aside fluoxetine, as well as old age of the patient, she was diagnosed with serotonin syndrome. Treatment was carried out after discontinuation of fluoxetine and buspirone, restriction of fluid therapy, as well as prescription of sodium chloride 5%, cyproheptadine, and diazepam. Conclusions: Consumers of SSRIs are at a higher risk of hyponatremia compared to those taking other antidepressants, especially if they are simultaneously treated by diuretics. Hyponatremia and SIADH need to be considered if a patient experiences disorientation receiving SSRIs. Physicians should be aware of the probability of acute hyponatremia and serotonin syndrome secondary to SSRIs in simultaneous use of fluoxetine and buspirone with diuretics. Moreover, physicians should note that serotonin toxicity is dose-dependent rather than idiosyncratic.

Buspirone for the treatment of dementia with behavioral disturbance.

Behavioral disturbances are common but serious symptoms in patients with dementia. Currently, there are no FDA approved drugs for this purpose. There have been case reports and small case series of the use of buspirone. In this retrospective study, we review 179 patients prescribed buspirone for treatment of behavioral disturbance in dementia to better characterize the efficacy and potential side effects. All patients prescribed buspirone for behavioral disturbance due to dementia from a geropsychiatric outreach program were reviewed. Data was collected and analyzed using SPSS. One hundred-seventy-nine patients met criteria for the study with a mean age of 83.8 + 7. Alzheimer's dementia was the most common dementia (n = 61; 34.1%) followed by mixed dementia (n = 50, 27.9%) then vascular type (n = 31; 17.3%). Behavioral disturbances were mainly verbal aggression (n = 125; 69.8%), and physical aggression (n = 116; 64.8%). Using the Clinical Global Impression scale, 68.6% of patients responded to buspirone, with 41.8% being moderately to markedly improved. The mean dose of buspirone was 25.7 mg ± 12.50. Buspirone appears to be effective in treating behavioral disturbances in dementia. Future prospective and double blinded studies are needed.

Inhibition of Reinforcing, Hyperalgesic, and Motor Effects of Morphine by Buspirone in Rats.

The present study shows an important role of serotonin-1A receptors in morphine-induced hyperalgesia and addiction. It shows that buspirone, a prescription medicine for anxiety and depression can block addictive and hyperalgesic effects of morphine. Clinicians should consider buspirone as adjunctive therapy with morphine to improve therapeutic medications in pain.

Nucleus incertus contributes to an anxiogenic effect of buspirone in rats: Involvement of 5-HT1A receptors

The nucleus incertus (NI), a brainstem structure with diverse anatomical connections, is implicated in anxiety, arousal, hippocampal theta modulation, and stress responses. It expresses a variety of neurotransmitters, neuropeptides and receptors such as 5-HT1A, D2 and CRF1 receptors. We hypothesized that the NI may play a role in the neuropharmacology of buspirone, a clinical anxiolytic which is a 5-HT1A receptor partial agonist and a D2 receptor antagonist. Several preclinical studies have reported a biphasic anxiety-modulating effect of buspirone but the precise mechanism and structures underlying this effect are not well-understood. The present study implicates the NI in the anxiogenic effects of a high dose of buspirone. Systemic buspirone (3 mg/kg) induced anxiogenic effects in elevated plus maze, light-dark box and open field exploration paradigms in rats and strongly activated the NI, as reflected by c-Fos expression. This anxiogenic effect was reproduced by direct infusion of buspirone (5 μg) into the NI, but was abolished in NI-CRF-saporin-lesioned rats, indicating that the NI is present in neural circuits driving anxiogenic behaviour. Pharmacological studies with NAD 299, a selective 5-HT1A antagonist, or quinpirole, a D2/D3 agonist, were conducted to examine the receptor system in the NI involved in this anxiogenic effect. Opposing the 5-HT1A agonism but not the D2 antagonism of buspirone in the NI attenuated the anxiogenic effects of systemic buspirone. In conclusion, 5-HT1A receptors in the NI contribute to the anxiogenic effect of an acute high dose of buspirone in rats and may be functionally relevant to physiological anxiety.

Occupancy of Dopamine D3 and D2 Receptors by Buspirone: A [11C]-(+)-PHNO PET Study in Humans.

There is considerable interest in blocking the dopamine D3 receptor (DRD3) versus the D2 receptor (DRD2) to treat drug addiction. However, there are currently no selective DRD3 antagonists available in the clinic. The anxiolytic drug buspirone has been proposed as a potential strategy as findings suggest that this drug has high in vitro affinity for DRD3, binds to DRD3 in brain of living non-human primate, and also disrupts psychostimulant self-administration in preclinical models. No study has explored the occupancy of DRD3 by buspirone in humans. Here, we used positron emission tomography (PET) and the D3-preferring probe, [(11)C]-(+)-PHNO, to test the hypothesis that buspirone will occupy (decreases [(11)C]-(+)-PHNO binding) the DRD3 more readily than the DRD2. Eight healthy participants underwent [(11)C]-(+)-PHNO scans after single oral dose administration of placebo and 30, 60, and 120 mg of buspirone in a single-blind within-subjects design. [(11)C]-(+)-PHNO binding in DRD2- and DRD3-rich areas was decreased by the highest (60-120 mg), but not the lowest (30 mg), doses of buspirone. The maximal occupancy obtained was ~25% in both areas. Plasma levels of prolactin (a DRD2 marker) correlated with percentage occupancy after orally administered buspirone. Self-reported dizziness and drowsiness increased after buspirone but that did not correlate with receptor occupancy in any region. Overall, the modest occupancy of DRD2 and DRD3 even at high acute doses of buspirone, yielding high levels of metabolites, suggests that buspirone may not be a good drug to preferentially block DRD3 in humans.

The influences of aconitine, an active/toxic alkaloid from aconitum, on the oral pharmacokinetics of CYP3A probe drug buspirone in rats.

Aconitine (AC), an active/toxic alkaloid from Aconitum species, is commonly present in Traditional Chinese Medicine (TCM) prescriptions because of the great effectiveness of Aconitum for the treatment of rheumatoid arthritis, cardiovascular diseases, and tumors in clinic. Buspirone (BP) is a sensitive CYP3A probe drug that is administered through oral/intravenous routes as recommended by the U.S. Food and Drug Administration. This study aims to investigate the influences of AC (0.125 mg/kg, oral) on first-pass (intestinal and hepatic) CYP3A activity by using oral BP as the probe in rats. The pharmacokinetics of oral buspirone hydrochloride at different doses (12.5, 25, and 50 mg/kg) were conducted. The pharmacokinetics of oral BP in rats pretreated with single dose or multiple doses (7-day) of AC were investigated. The plasma concentrations of BP and its major metabolites [1-(2-pyrimidinyl)piperazine (1-PP) and 6'-hydroxybuspirone (6'-OH-BP)] were determined. The formation ratios of 1-PP and 6'-OH-BP from BP (AUC0-∞ of 1-PP/AUC0-∞ of BP and AUC0-∞ of 6'-OH-BP/AUC0-∞ of BP values) showed no alternation when the dose of BP changed. Single dose of AC decreased the AUC0-∞ of BP by 53% but increased the formation ratio of 6'-OH-BP by 74% (P<0.05). Multiple AC exposure increased the AUC0-∞ of BP by 110%, and the formation ratios of 1-PP and 6'-OH-BP from BP were increased by 229% and decreased by 95%, respectively (P<0.05). Conclusively, single/multiple AC exposure did not alter the first-pass CYP3A activity when using oral BP as probe in rats. Nevertheless, multiple AC exposure had markedly changed the production of BP metabolites.

Dose dependent effects of serotonergic agents on anxiety.

The role of serotonin in depression and anxiety is still highly controversial. In this experiment the effect of two substances upon anxiety was studied in rats. Forty adult (45-55 weeks old) male Wistar rats were used to study the following behavioral parameters on elevated plus maze test: open arm and closed arm entries; open arm, closed arm and central square activity duration, open arm preference and total distance traveled. A single injected dose of the antidepressant fluoxetine had no significant effect on animals' activity in the open-arm test, neither in a small dosage (5 mg/kgbw) nor in a higher one (10 mg/kgbw), whereas a single high dose of buspirone significantly impeded the open-arm activity of the rats. None of the substances influenced the general locomotor activity significantly, but the higher doses of buspirone mainly blocked the closed-arm entries and they even decreased the total distance traveled. Acute fluoxetine and buspirone administration influenced the rats' behavior in the elevated plus-maze test in a dose dependent manner. Anxiolytic effects occur after small doses but anxiogenic-like effects were noticed in rodents when higher doses were used.

A Randomized Double-Blind Placebo-Controlled Clinical Trial of Adjuvant Buspirone for Irritability in Autism

BackgroundThe brain serotonin level is decreased in individuals with autism. Buspirone is a 5-HT(1A) receptor agonist with antiaggressive effects increasing prosocial behaviors. MethodsWe conducted an 8-week randomized double-blind placebo-controlled clinical trial. Participants included 40 outpatient children and adolescents with autism. The patients took buspirone plus risperidone or risperidone plus placebo during 8 weeks. The patients were assessed at baseline, week 4, and week 8 using the Aberrant Behavior Checklist-Community Rating Scale. ResultsEighteen patients in the placebo group and 16 patients in the buspirone group completed this trial. The mean dose of buspirone was 6.7 (SD 2.7) mg/day. Irritability subscale score significantly decreased during this trial in both groups (buspirone group: declined from 25.7 [SD 5.7] to 16.3 [SD 8.5]; placebo group: declined from 24.7 [SD 7.6] to 18.2 [SD 7.7]). The Cohen d effect size was .45. Thirteen (81.2%) of 16 patients in the buspirone group and 7 (38.9%) of 18 patients in the placebo group showed a ≥30% decline in irritability score. The relative risk for treatment was 2.1. There were no serious adverse effects. The most common adverse effects in the buspirone group were increased appetite, drowsiness, and fatigue. ConclusionThis clinical trial supports that low dose buspirone plus risperidone is more effective than risperidone plus placebo for treating irritability in individuals with autism.

Inhibition of apomorphine-induced conditioned place preference in rats co-injected with buspirone: Relationship with serotonin and dopamine in the striatum

Apomorphine is a non-narcotic derivative of morphine, which acts as a dopamine agonist to produce psychostimulant like effects. Currently, apomorphine is used in patients with advanced Parkinson׳s disease, for the treatment of persistent and disabling motor fluctuations, but a constellation of addictive syndromes such as excessive over use of medication, compulsive behaviors, and disturbances of impulse control are noticed in certain patients. Research on rodent models using conditioned place preference (CPP) paradigm also shows that the drug is rewarding. Previously we have shown that repeated administration of apomorphine produces behavioral sensitization which is prevented in rats co-injected with a low (1.0mg/kg) but not higher (2.0mg/kg) dose of buspirone. The present study shows that rewarding effects of apomorphine (1.0mg/kg) in a CPP paradigm are also blocked in rats co-injected with a low (1.0mg/kg) but not higher (2.0mg/kg) dose of buspirone. The levels of serotonin and its metabolite are decreased in the caudate as well as nucleus accumbens of rats exhibiting CPP and the decreases do not occur in animals co-injected with low or higher dose of buspirone. The levels of dopamine and its metabolites are not affected in animals exhibiting CPP; administration as well as co-administration of higher dose of buspirone decreased dopamine metabolism in the caudate as well as nucleus accumbens. The findings suggest a critical role of serotonin in the rewarding effects of apomorphine and imply that co-use of buspirone at low doses can help to control addictive syndromes in Parkinson׳s disease patients on apomorphine therapy.

Effects of Buspirone on Behavior in Female Mice in a Social Discomfort Model

We report here studies of the effects of single and chronic (14 days) administration of buspirone (1 mg/kg, i.p.) on the behavior of female C57BL/6J mice in conditions of social discomfort induced by prolonged periods of time in a cage with an aggressive male on the other side of a perforated partition and the presence at daily intermale confrontations. These experiments showed that in conditions of social discomfort, female mice showed dynamic changes in the sensitivity of brain 5-HT1A receptors, assessed in terms of the animals’ behavior 30 min after single doses of buspirone. Sensitivity was found to increase at the initial stages of formation of pathological behavior (10 days) and to decrease at 20‐30 days. Females with decreased 5-HT1A receptor sensitivity due to 30 days of living in conditions of social discomfort also demonstrated decreased sensitivity to chronic administration of buspirone.