Biomedical subjects

Michel Bourin

Publications and source records attributed to Michel Bourin.

At least 37 records · Page 2Linked to original sources

PubMed2005

A review of clozapine safety.

Clozapine is a distinctive antipsychotic agent, having a unique clinical profile and an idiosyncratic safety profile. More so than with other agents, the weighting of its adverse event profile is critical, in order to counterbalance its clear clinical advantages. The safety issues with clozapine are in a number of areas, some of which are considered medical emergencies and potentially life-threatening. These include haematological (neutropenia and agranulocytosis), CNS (seizures), cardiovascular (myocarditis and cardiomyopathy), metabolic (diabetes), gastrointestinal and neuromuscular. Understanding the safety profile of clozapine allows an informed use of the agent that can maximise its clear clinical benefit and minimise the known risks.

Antipsychotic Agents↗

PubMed2005

Evidence for the activity of lamotrigine at 5-HT(1A) receptors in the mouse forced swimming test.

BACKGROUND: The antiepileptic drug lamotrigine is effective in the treatment of focal epilepsies. It is thought to act by inhibition of glutamate release through blockade of voltage-sensitive sodium channels and stabilization of the neuronal membrane. Lamotrigine is also effective in the treatment of mood disorders such as bipolar disorder. However, its exact mechanism of action in these conditions remains unclear. The aim of the present study was to evaluate the antidepressant-like effect of lamotrigine in a mouse model of depression, namely the forced swimming test (FST). Association studies using specific and nonspecific ligands acting on serotonin (5-hydroxytryptamine; 5-HT1) receptor subtypes were undertaken to evaluate the potential role of these receptors in the anti-immobility effect of lamotrigine. METHODS: The mouse FST was performed after single administration of lamotrigine. Subactive doses of lamotrigine were administered in association with subactive doses of the following 5-HT1 receptor agonists or antagonists: 8-hydroxy-2-(di-n-propilamino)-tetralin (8-OH-DPAT, a standard 5-HT(1A) receptor selective agonist), pindolol (a presynaptic and postsynaptic 5-HT(1A/1B) receptor antagonist), NAN-190 (a 5-HT(1A) receptor antagonist), RU 24969 (a 5-HT(1A/1B) receptor agonist) and anpirtoline (5-HT(1B) agonist). RESULTS: Lamotrigine impaired spontaneous locomotor activity at doses of 4 mg/kg or greater, and activity decreased by more than 50% at the 16 mg/kg dose. When administered alone, lamotrigine (8 and 16 mg/kg) decreased immobility time in the FST. Only 8-OH-DPAT (1 mg/kg), pindolol (32 mg/kg) and RU 24969 (0.5 mg/kg) enhanced the antidepressant-like effect of lamotrigine in the FST. CONCLUSIONS: These results suggest that postsynaptic 5-HT(1A) receptors might be involved in the activity of lamotrigine. Furthermore, they demonstrate that lamotrigine more closely resembles valproate and carbamazepine than lithium, with the advantage of an anti-immobility effect in the mouse FST when administered on its own.

Animals↗

PubMed2004

Implication of 5-HT2 receptor subtypes in the mechanism of action of antidepressants in the four plates test.

RATIONALE: The selective serotonin reuptake inhibitors (SSRIs) and the serotonin and noradrenaline reuptake inhibitors (SNRIs) increase synaptic levels of serotonin, leading to an increased activation of a multitude of specific postsynaptic 5-HT receptors. However, it is not yet known which 5-HT receptor subtypes mediate the therapeutic effects of antidepressants. METHODS: The effects of the SSRI, paroxetine and the SNRI, venlafaxine were evaluated in the mouse four plates test (FPT). RESULTS: Paroxetine administered intraperitoneally (IP) (0.5, 2-8 mg/kg) potently augmented the number of punished passages accepted by mice in this paradigm. The effects of paroxetine (8 mg/kg) were not reversed by the selective 5-HT2C receptor antagonist, RS 10-2221 (0.1 mg/kg and 1 mg/kg) or the selective 5-HT2B/2C receptor antagonist SB 206553 (0.1 mg/kg and 1 mg/kg), at doses which lack an effect when administered alone. In contrast, the selective 5-HT2A receptor antagonist, SR 46349B (0.1 mg/kg and 1 mg/kg) completely abolished the paroxetine-induced increase in punished passages. The acute administration of venlafaxine induced an anxiolytic-like effect in the FPT at the doses of 2-16 mg/kg. This effect was reversed by the 5-HT2B/2C receptor antagonist as did SR 46349B, for both doses administered. Our results strongly suggest that activation of 5-HT2A receptors is critically involved in the anxiolytic activity of paroxetine, whereas the 5-HT2A and 5-HT2B receptors are involved in the anti-punishment action of venlafaxine in the FPT. The co-administration of selective 5-HT2A, 2B, 2C receptor agonists (DOI, 0.06 mg/kg and 0.25 mg/kg; BW 723C86, 0.5 mg/kg and 2 mg/kg and RO 60-0175, 0.06 mg/kg and 0.25 mg/kg), respectively, was subsequently investigated. The effects of sub-active doses of paroxetine (0.25 mg/kg and 1 mg/kg) were augmented by BW 723C86 and RO 60-0175 receptor agonist challenge. The anti-punishment effects of venlafaxine (0.25 mg/kg and 1 mg/kg) were potentialised only by DOI co-administration. CONCLUSION: These results indicate that the co-administration of 5-HT2 receptor agonists with paroxetine and venlafaxine may provide a powerful tool for enhancing the clinical efficacy of these antidepressants.

Animals↗

PubMed2004

Forced swimming test in mice: a review of antidepressant activity.

RATIONALE: Among all animal models, the forced swimming test (FST) remains one of the most used tools for screening antidepressants. OBJECTIVE: This paper reviews some of the main aspects of the FST in mice. Most of the sensitivity and variability factors that were assessed on the FST are summarized. MECHANISMS: We have summarized data found in the literature of antidepressant effects on the FST in mice. From this data set, we have extrapolated information on baseline levels of strain, and sensitivity against antidepressants. RESULTS: We have shown that many parameters have to be considered in this test to gain good reliability. Moreover, there was a fundamental inter-strain difference of response in the FST. CONCLUSIONS: The FST is a good screening tool with good reliability and predictive validity. Strain is one of the most important parameters to consider. Swiss and NMRI mice can be used to discriminate the mechanisms of action of drugs. CD-1 seems to be the most useful strain for screening purposes, but this needs to be confirmed with some spontaneous locomotor activity studies.

Animals↗

PubMed2004

No relationship between high nevirapine plasma concentration and hepatotoxicity in HIV-1-infected patients naive of antiretroviral treatment or switched from protease inhibitors.

OBJECTIVE: A prospective population pharmacokinetic study of nevirapine (NVP) was performed to test the relationship between hepatotoxicity and NVP trough plasma concentration and to identify which covariates could influence NVP pharmacokinetics. METHODS: All patients [77 HIV-1 (human immunodeficiency virus type 1)-infected patients (128 samples)] were either on first-line antiretroviral therapy or switched from successful therapy containing protease inhibitor. Population pharmacokinetic parameters were estimated by a non-linear mixed-effect modelling method. Hepatotoxicity was evaluated by ASAT (aspartate aminotransferase) plasma level. RESULTS: No correlation was found between high NVP trough plasma concentration and high ASAT level or the increase of ASAT level on NVP therapy. Age and Caucasian race were found to be significant covariates of NVP clearance (Cl/F). Population pharmacokinetic parameters (rate absorption constant=1.04 h(-1); Cl/F=3.31 h(-1); apparent volume of distribution=92 l) are consistent with previous studies. CONCLUSION: High NVP trough plasma concentrations are not correlated with hepatotoxicity in our population. NVP clearance is decreased in the elderly patients, suggesting a potential increase of NVP plasma level and the interest of therapeutic drug monitoring for this population.

Anti-HIV Agents↗

PubMed2004

Phenotype and genotype for thiopurine methyltransferase activity in the French Caucasian population: impact of age.

OBJECTIVE: Thiopurine drugs are commonly used in pediatric patients for the treatment of acute leukemia, organ transplantation and inflammatory diseases. They are catabolized by the cytosolic thiopurine methyltransferase (TPMT), which is subject to a genetic polymorphism. In children, enzyme activities are immature at birth and developmental patterns vary widely from one enzyme to another. The present study was undertaken to evaluate erythrocyte TPMT activity and the correlation between genotype and phenotype in different age groups from birth to adolescence and adulthood. METHODS: The study included 304 healthy adult blood donors, 147 children and 18 neonates (cord bloods). TPMT activity was measured by liquid chromatography, and genotype was determined using a polymerase chain reaction reverse dot-blot analysis identifying the predominant TPMT mutant alleles (TPMT*3A, TPMT*3B, TPMT*3C, TPMT*2). RESULTS: There was no significant difference in TPMT activity between cord bloods ( n=18) and children ( n=147) (17.48+/-4.04 versus 18.62+/-4.14 respectively, P=0.424). However, TPMT was significantly lower in children than in adults (19.34+/-4.09) ( P=0.033). In the whole population, there were 91.9% homozygous wild type, 7.9% heterozygous mutants and 0.2% homozygous mutants. The frequency of mutant alleles was 3.0% for TPMT*3A, 0.7% for TPMT*2 and 0.4% for TPMT*3C. CONCLUSION: No impact of child development on TPMT activity could be evidenced, suggesting that TPMT activity is already mature at birth. The difference between children and adults was low with reduced clinical impact expected. When individual TPMT activity was compared with genotype, there was an overlapping region where subjects (4.5%, 12 adults, 9 children) were either homozygous wild type or heterozygous, with a TPMT activity below the antimode value. This result highlighted the importance of measuring TPMT activity to detect all patients at risk of thiopurine toxicity.

Adult↗

PubMed2004

Different pathways mediated by CCK1 and CCK2 receptors: effect of intraperitonal mrna antisense oligodeoxynucleotides to cholecystokinin on anxiety-like and learning behaviors in rats.

Cholecystokinin (CCK) and its analogs generate anxiety in humans and measurable anxiety-like behaviors in rats. CCK receptor blockers have been reported to have variable effects in the treatment of anxiety disorders. In a prior study, intracerebroventricular administration of CCK-antisense oligodeoxynucleotides (ASODN) for 3 days significantly diminished anxiety-like behavior in rats. Counter to our expectations, intraperitoneal (i.p.) administration of CCK-ASODN significantly increased anxiety-like behavior and impaired retention performance in the Morris water maze. The aim of the present study was to manipulate CCK-mediated anxiety-like behavior and spatial memory in rats by peripheral (i.p.) administration of ASODN to preproCCK in the presence of antagonists to CCK1 and CCK2 receptor subtypes to further elucidate the roles of these two receptors and better understand the effects of i.p. CCK-ASODN. CCK-ASODN was injected i.p. to rats five times at 24-hr intervals with and without administration of CCK1R antagonist PD135158 or CCK2 antagonist benzotrip. Control groups received injections of either a scrambled oligodeoxynucleotide (ScrODN) or vehicle. On Day 6, the rats were assessed in the elevated plus maze paradigm and in the Morris water maze. The rats were sacrificed and their blood was assessed for corticosterone, ACTH, and prolactin levels. The results show that i.p. CCK-ASODN significantly increased anxiety-like behavior and impaired retention performance in the Morris water maze, compared to both control groups, accompanied by increased plasma corticosterone and plasma ACTH concentrations. In contrast, administration of CCK-ASODN together with CCK2R antagonist, but not with CCK1R antagonist, significantly decreased anxiety-like behavior in rats, but still impaired retention performance in the Morris water maze paradigm. Lower levels of plasma corticosterone and ACTH in CCK-ASODN+CCK2R antagonist-treated rats accompanied the reduced anxiety-like behavior. The present study showed an anxiolytic effect of i.p. CCK-ASODN in the presence of CCK2R, but not CCK1R.

Adrenocorticotropic Hormone↗

PubMed2004

Sedation, an unpleasant, undesirable and potentially dangerous side-effect of many psychotropic drugs.

Sedation is a property of many psychotropic drugs. It can be defined as a decrease in psychomotor and cognitive performance. Many of the earlier neuroleptic, anxiolytic, antidepressant and antihistamine drugs were extremely sedative and sedation came to be considered as an integral part of the activity of these compounds. Newer, far less sedative, examples of each of these classes have shown that sedation is not required for their efficacy. Sedation is now increasingly considered as an adverse effect which should be avoided rather than a desirable effect especially when treating disorders such as anxiety or depression. This article discusses the sedative properties and mechanisms of different classes of psychotropic drugs.

Animals↗

PubMed2004

Anxiolytic profile of HG1, a 5-HT-moduline antagonist, in three mouse models of anxiety.

HG1 is a new 5-HT-moduline antagonist which is itself an endogenous tetrapeptide specifically acting as an antagonist of 5-HT(1B) auto- and heteroreceptors. Blockade of endogenous 5-HT-moduline might provoke anxiolysis, so it could be a new therapeutic target in anxiety disorders. The aim of our study was to examine the effects of HG1 in three mouse models of anxiety: the four plates test (FPT), the black and white (B&W) model and the elevated plus maze (EPM). Male Swiss mice were intraperitoneally and acutely administered HG1 at the doses of 8, 16, 32 and 64 mg/kg. In these three tests, HG1 exhibited an anxiolytic profile similar to that of diazepam, the referential benzodiazepine compound, without affecting locomotor activity. In the three models used, HG1 was as efficient as benzodiazepine and may consequently exert its anxiolytic effects via the GABA-ergic system. We cannot exclude that it might also act through 5-HT receptors and rather have the profile of a selective serotonin reuptake inhibitor.

Animals↗

PubMed2004

Is dopamine a limiting factor of the antidepressant-like effect in the mouse forced swimming test?

To study the role of dopamine (DA) in antidepressant-like effect in the forced swimming test (FST), the relationship between the magnitude of the antidepressant-like effect of drugs [citalopram, fluoxetine, paroxetine (selective serotonin reuptake inhibitors), desipramine (tricyclic antidepressant), maprotiline (tetracyclic antidepressant), bupropion (DA reuptake inhibitor), and tranylcypromine (inhibitor of monoamine oxidase)] and the corresponding concentration of DA in the whole brain of mice was investigated. A trend for an inversely proportional linear relationship [(magnitude of the antidepressant-like effect) = -0.0145 x (concentration of DA in the whole brain) +34.773 (r = 0.276)] was observed between the magnitude of the antidepressant-like effect and the concentrations of DA in the whole brain, but this correlation was not significant. This result suggests that the high concentration of DA in the whole brain could be a limiting factor for the antidepressant-like effect of antidepressants such as tranylcypromine and seems to play a minor role in the antidepressant-like activity of another antidepressant such as bupropion in the FST.

Animals↗

PubMed2004

Mean Deviation of Inter-rater Scoring (MDIS): a simple tool for introducing conformity into groups of clinical investigators.

In spite of considerable progress over the past decade, training investigators for inter-rater reliability for clinical trials remains a major problem. The aim of the present study was to promote a new tool to increase data homogeneity by introducing conformity into groups of clinical investigators. The investigators scoring grid we are proposing-the Mean Deviation of Inter-rater Scoring (MDIS)-involves the calculation of the score deviation for each investigator relative to the median score of an expert group who had evaluated the same videotape-recorded clinical case. Whatever the scale, the score deviation is calculated as the absolute deviation value from the median score obtained by the experts for each item. The MDIS value is then evaluated from all the scores given by an investigator by dividing the total sum of the previously defined values by the number of items of the scale. Some examples from practice are given using several rating scales: (i) Hamilton Anxiety Rating Scale; (ii) Hamilton Depression Rating Scale; (iii) Montgomery Asberg Depression Rating Scale; and (iv) Positive And Negative Symptoms Scale. Finally, such a method could also be employed by experts to evaluate the quality of videotape-recorded clinical cases used in clinical trials, as well as by teachers to evaluate initial or continuous medical training.

Anxiety Disorders↗

PubMed2004

Deletion of the CCK2 receptor gene reduces mechanical sensitivity and abolishes the development of hyperalgesia in mononeuropathic mice.

Previous studies suggest that cholecystokinin (CCK) is implicated in the modulation of pain sensitivity and the development of neuropathic pain. We used CCK(2) receptor deficient (CCK(2) (-/-)) mice and assessed their mechanical sensitivity using Von Frey filaments, as well as the development and time course of mechanical hyperalgesia in a model of neuropathic pain. We found that CCK(2) (-/-) mice displayed mechanical hyposensitivity, which was reversed to the level of wild-type animals after administration of naloxone (0.1-10 mg/kg). On the other hand, injection of L-365260 (0.01-1 mg/kg), an antagonist of CCK(2) receptors, decreased dose-dependently, mechanical sensitivity in wild-type mice. The mechanism of reduced mechanical sensitivity in CCK(2) (-/-) mice may be explained by changes in interactions between CCK and opioid systems. Indeed, CCK(2) (-/-) mice natively expressed higher levels of lumbar CCK(1), opioid delta and kappa receptors. Next, we found that CCK(2) (-/-) mice did not develop mechanical hyperalgesia in the Bennett's neuropathic pain model. Induction of neuropathy resulted in decrease of lumbar pro-opiomelanocortin (POMC) gene expression in wild-type mice, but increase of POMC expression in CCK(2) (-/-) mice. In addition, induction of neuropathy resulted in further increase of opioid delta receptor in CCK(2) (-/-) mice. Gene expression results indicate up-regulation of opioid system in CCK(2) (-/-) mice, which apparently result in decreased neuropathy score. Our study suggests that not only pain sensitivity, but also mechanical sensitivity and the development of neuropathic pain are regulated by antagonistic interactions between CCK and opioid systems.

Animals↗

PubMed2004

Dopamine, depression and antidepressants.

Abstract The relationship between depression and dopamine deficiency in the mesolimbic pathway has been hypothesized for many years. The experimental studies with animal models of depression and the human studies implicate the role of the dopamine system in depression. Not only do dopaminergic receptor agonists, but also antagonists such as olanzapine exhibit antidepressant effects associated with standard antidepressants in patients with treatment-resistant depression. This paradoxical result suggests that further investigations are necessary to understand the role played by dopamine in depression.

Animals↗

PubMed2004

Does rat global transient cerebral ischemia serve as an appropriate model to study emotional disturbances?

We used two validated psychopharmacological methods, the forced swimming test (FST 20 min and 5 min) and the elevated plus-maze (EPM), to quantify depression-like and anxiety-like behavior induced by transient global cerebral ischemia in the rat. We also validated use of these methods for the study of antidepressant (imipramine) and anti-anxiety drugs (diazepam). Twelve days after surgery to provoke transient global ischemia, spontaneous motor activity was 40% higher in ischemic rats than in sham-operated controls. Duration of immobility during the FST 20 min and 5 min was 28 and 30% shorter, respectively, than in controls. Treatment with imipramine (3 x 30 mg/kg i.p.) induced a significantly shorter duration of immobility during the FST 5 min, but with no difference between ischemia and control rats. The EPM demonstrated that ischemia did not induce any change in the six behavior parameters measured. Diazepam (1.5 mg/kg i.p.) induced significant anxiolytic effects which were similar in ischemic and sham-operated animals. Both tests failed to demonstrate perturbed performance but conversely, these findings did disclose the sensitivity of ischemia-exposed rats to the action of imipramine and diazepam, demonstrating the usefulness of these tests as psychopharmocological tools for evaluating the effect of psychotropics in the ischemic rat.

Animals↗

PubMed2004

Preclinical and clinical pharmacology of cyamemazine: anxiolytic effects and prevention of alcohol and benzodiazepine withdrawal syndrome.

Several studies have suggested that the antipsychotic compound, cyamemazine, possesses anxiolytic properties in humans. The original pharmacological profile of cyamemazine (D(2), 5-HT(2A), 5-HT(2C), and 5-HT(3) receptor antagonist), which was established by binding, microdialysis and behavioral studies, is consistent with these observations. In the light/dark exploration test, cyamemazine demonstrated anxiolytic-like activity by acute, but not chronic administration. By chronic administration, however, cyamemazine increased the time spent in the open arms of the elevated plus maze (EPM) test demonstrating anxiolytic-like activity. The discrepancy between the results obtained in these tests by acute and chronic administration, could be due to a combination of dopamine D(2) receptor antagonism with antagonism of the 5-HT(2C) and 5-HT(3) receptors. The action of cyamemazine on both the dopaminergic system and 5-HT(3) receptors could also explain the activity of cyamemazine in the management of alcohol withdrawal demonstrated in preclinical studies. This potential indication for cyamemazine and its activity in benzodiazepine withdrawal syndrome have recently been investigated in clinical trials and the results of these studies are presented in this review.

Alcohols↗

PubMed2004

Nicotinic receptors and schizophrenia.

The incidence of smoking is very high in non-schizophrenic subjects presenting various psychiatric disorders (35 to 54%). However, the incidence of smoking is extremely high in schizophrenic patients: 80% to 90%, versus 25% to 30% of the general population. Various studies have demonstrated that the use of tobacco transiently restores the schizophrenic patient's cognitive and sensory deficits. Smoking cessation also appears to exacerbate the symptoms of the disease. Post-mortem binding studies have revealed a disturbance of nicotinic receptor expression, affecting the alpha(7) and alpha(4)beta(2) subunits, in various cerebral areas. Genetic linkage studies have also shown that the alpha(7) subunit is involved in schizophrenia. This review assesses the involvement of the nicotinic system in schizophrenia and suggests ways in which this system may participate in the pathophysiology of this disease.

Cognition↗

PubMed2004

Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors.

OBJECTIVE: To study agomelatine (S 20098), a potent agonist at melatonin receptors and antagonist at serotonin-2C (5-HT(2C)) receptors, in an animal model of depression, namely, the rodent forced swimming test (FST). METHODS: The effects of acute and repeated administration of S 20098 were compared with those of melatonin (4, 8, 16, 32, 64 mg/kg intraperitoneally [IP] for mice), imipramine (64 mg/kg orally for rats, 8 mg/kg IP for mice) and fluoxetine (16 mg/kg IP for mice). The influence of the pretreatments with 5-HT(1A) or 5-HT(1B) receptor agonists (8-OH-DPAT, anpirtoline) and 5-HT(1A/1B), 5-HT(2A/2C) or 5-HT(3) antagonists (pindolol, ritanserin, ondansetron) on the effects of S 20098 or melatonin were compared with imipramine and fluoxetine in mice. RESULTS: Acute or repeated (13 days) administration of S 20098 or imipramine in rats significantly decreased the duration of immobility during the FST at all doses. A dose-dependent effect was observed after the repeated treatment with S 20098. When given for 10 days to mice in the evening, S 20098 was active on the FST at doses of 4, 16 and 32 mg/kg, whereas the acute administration of S 20098 (in the morning and evening) was without any significant effect. Acute or repeated administration of S 20098 did not modify the locomotor activity of mice. The combination of S 20098 with the above-mentioned pretreatments enhanced the effects of S 20098, given alone, on the duration of immobility. By comparison, acute melatonin was inactive in the FST and only pretreatment with 8-OH-DPAT or pindolol revealed an anti-immobility effect. A pretreatment with 8-OH-DPAT also induced anti-immobility effects with imipramine, but not fluoxetine, whereas pindolol exerted additive effects with fluoxetine but not imipramine. CONCLUSION: These results demonstrate the antidepressant-like activity of repeated administration of S 20098 in the FST. Moreover, the combination of 5-HT agonists and antagonists leads to more powerful effects with S 20098 than with melatonin, thereby emphasizing the contribution of 5-HT receptors to the antidepressant activity of S 20098. Compared with imipramine and fluoxetine, the 5-HT receptor subtypes that may be involved in the antidepressant-like activity of S 20098 are not similar. Indeed, when considering the binding properties of S 20098, the 5-HT(2C) receptor subtype appears to be the most attractive candidate. It is concluded that the antidepressant-like activity of S 20098 in this model most probably involves a combination of both its melatonin agonist and 5-HT(2C )receptor antagonist properties.

Acetamides↗

PubMed2003

Evidence for a 5-HT2A receptor mode of action in the anxiolytic-like properties of DOI in mice.

DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] displays a high affinity for the rat 5-HT2A, 5-HT2B and 5-HT2C receptors (pKi 7.3, 7.4 and 7.8, respectively) and acts as an agonist. DOI (0.5-4 mg/kg, i.p. 30 min pre-test) increased the number of punished passages in the mouse four plates test (FPT). The anti-punishment action of DOI (1 mg/kg, i.p. 30 min pre-test) was abolished by prior treatment with the selective 5-HT2A receptor antagonist SR 46949B (0.1 and 1 mg/kg, i.p. 45 min pre-test) but not by the selective 5-HT2C receptor antagonist RS 10-2221 (0.1 and 1 mg/kg, i.p. 45 min pre-test) nor the selective 5-HT2C/2B receptor antagonist SB 206553 (0.1 and 1 mg/kg, i.p. 45 min pre-test). An anxiolytic-like action was also observed for DOI (1 mg/kg) in the elevated plus maze (EPM). The anxiolytic-like action of DOI (1 mg/kg, i.p. 30 min pre-test) was antagonised by pre-treatment with SR 46949B (0.125 and 0.5 mg/kg, i.p. 45 min pre-test) but not by RS 10-2221 (0.1 and 1 mg/kg, i.p. 45 min pre-test) nor SB 206553 (0.1 and 1 mg/kg, i.p. 45 min pre-test). In conclusion, DOI produced an anxiolytic-like profile in the mouse FPT and EPM. These effects are likely to be 5-HT2A receptor mediated.

Animals↗