José Francisco Navarro

Anxiogenic-like activity of L-655,708, a selective ligand for the benzodiazepine site of GABAA receptors which contain the alpha-5 subunit, in the elevated plus-maze test

GABAA receptor is a transmembrane hetero-oligomeric protein which consists of five subunits, the combination of which confers unique pharmacological properties to the receptor. L-655,708 is a new ligand selective for GABAA receptors containing an alpha-5 subunit. It is a partial inverse agonist that exhibits a 100-fold higher affinity for alpha-5 containing receptors, compared with alpha-1 containing receptors. The aim of this study was to examine the effects of L-655,708 (0.625–5 mg/kg ip) on anxiety tested in the elevated plus-maze in male mice. A number of classical parameters were collected: (a) Open arm duration; (b) Closed arm duration; (c) Central platform duration; (d) Open arm frequency; (e) Closed arm frequency; and (f) Total number of entries in the arms. Likewise, different ethological measures were also obtained (rears, head-dipping [HD], stretched attend posture [SAP] and grooming). Mice treated with L-655,708 showed a marked increase in the frequency of entries and the time spent in closed arms, as well as a reduction in the frequency of entries and the time spent in open arms, as compared with the control group. Unprotected HDs were also significantly decreased after treatment with the drug. Overall, these results indicate that L-655,708 could exhibit an anxiogenic-like profile in the elevated plus-maze test. This ligand is selective for GABAA receptors containing an alpha-5 subunit, which is mainly expressed over the hippocampal formation, a region which has been involved in the modulation of anxiety.

Acute and subchronic effects of MDMA ("ecstasy") on anxiety in male mice tested in the elevated plus-maze.

3,4-Methylenedioxymethamphetamine (MDMA) is a compound structurally similar to methamphetamine, which has become one of the most widely used illicit substances. Animal studies investigating acute effects of MDMA on anxiety are unclear since, although an anxiogenic-like action of MDMA in different animal models of anxiety has been mainly described, there is also evidence supporting an anxiolytic-like effect for this drug. An attempt was made to clarify the possible anxiogenic-like profile of MDMA (1, 8 and 15 mg/kg i.p.) by analyzing its effect on behavior of male mice in the elevated plus-maze test. Moreover, the possible development of tolerance to the effects of MDMA on anxiety after its subchronic administration for 5 consecutive days was examined. The parameters evaluated included: (1) total time in open arms, (2) total time in closed arms, (3) total time in central area, (4) number of open arm entries, (5) number of closed arm entries and (6) number of central area entries. Acute treatment with MDMA (8 mg/kg) significantly reduced the time spent in the open arms, as well as markedly increasing the number of entries in the closed arms and in the central area, as compared with the control group, suggesting that MDMA, at this dose, has an anxiogenic-like activity. Mice subchronically treated with the drug (1 and 8 mg/kg) displayed a notable reduction in the time spent in the open arms, accompanied by an increase in the time spent in the closed arms and in the central platform. These results indicate that the anxiogenic-like effect found after acute treatment is not only maintained but also more marked after subchronic treatment. In contrast, mice treated subchronically with the highest dose of MDMA (15 mg/kg) exhibited a significant increase in the time spent in the open arms as well as a marked reduction in the time spent in the closed arms, supporting an anxiolytic-like activity of the drug. A possible dual pharmacological property of MDMA on anxiety is suggested.

Effects of selective neuronal nitric oxide synthase inhibition on sleep and wakefulness in the rat

The role played by the unconventional messenger Nitric Oxide (NO) upon the sleep-wake cycle remains controversial. Evidence suggests a positive role of NO on Slow Wave Sleep (SWS) and Paradoxical Sleep (PS) regulation, favoring sleep. However, other studies have found a role of NO upon wakefulness and alertness, inhibiting sleep. Divergences have been explained in part because of the use of different inhibitors of nitric oxide synthases (NOS). The aim of this study is to analyse the effects of a highly selective neuronal NOS inhibitor (3-Bromo7-Nitroindazole) on sleep-wake states in rats. Male Wistar rats were stereotaxically prepared for polysomnography. 3-Bromo-7-Nitroindazole (10, 20, 40 mg/kg, i.p.) dissolved in DMSO 10% filled with saline, or vehicle (DMSO 10% in saline) was administered at the beginning of the light period. Three hours of polygraphic recordings were evaluated for stages of vigilance. Results show dose-dependent effects of 3-Bromo7-Nitroindazole upon sleep: 10 mg/kg decreases duration and number of episodes of deep SWS, increasing duration of light SWS. 20 mg/kg decreased duration of light and deep SWS, while active and quiet wake increased. Deep SWS and PS latency increased. Number of episodes of PS decreased, as well as number of cycles of sleep and time spent asleep. 40 mg/kg reduced duration of deep SWS and increased mean episode duration of light SWS. Therefore, sleep states are affected by selective inhibition of nNOS, reducing in all cases deep SWS. These results support the hypothesis that nitric oxide, produced by nNOS, is involved in sleep processes, favoring sleep.

Effect of low doses of clozapine on behaviour of isolated and group-housed male mice in the elevated plus-maze test

Clozapine is effective over a low and narrow dose range in the treatment of the negative symptoms of schizophrenia. Its efficacy is said to reflect an anxiolytic property of the neuroleptic. This study examined the effects of a low dose range of clozapine (0.1, 0.2 and 0.4 mg/kg) administered to isolated (7 days) and group-housed male mice on their behaviour in the elevated plus-maze. The results using this model of anxiety showed no dose-dependent effect on behaviour after treatment with low doses of clozapine. Some doses (0.1 and 0.4 mg/kg), however, reduced the duration and frequency of open arm entries compared to control-treated mice in the group-housed animals. This might indicate a slight anxiogenic effect. Support for this view is provided by some of the ethological measures, particularly head-dipping (HD). Seven days of isolation did not alter the main anxiety indices in controls. Nevertheless, some measures (e.g. closed entries and duration in the closed arm) were modified by the clozapine treatment (0.2 mg/kg) in a manner suggesting a mild anxiogenic action. The effects of the drug in individually and group-housed male mice were certainly different.

Acute and Subchronic Effects of Tiapride on Isolation-Induced Aggression in Male Mice

Although the antiaggressive properties of several atypical neuroleptics are known, the actions of tiapride (a selective dopaminergic D2-receptor antagonist) on agonistic behavior have not been explored and there are no studies comparing acute and subchronic effects of this compound on aggression in rodents. In this work, the effects of tiapride (20–100 mg/kg, IP), administered acutely or subchronically for 10 days, on agonistic behaviour elicited by isolation in male mice were examined. Individually housed mice were exposed to anosmic “standard opponents” 30 min after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. Tiapride decreased time spent in offenssive behaviors significantly, without an impairment of motor activity (60 and 80 mg/kg). Moreover, no tolerance to tiapride antiaggressive activity was observed after repeated administration of the drug. On the contrary, the action on immobility showed a clear tolerance development with repeated injections (100 mg/kg). The divergence found in the temporal course of tolerance to tiapride in its antiaggressive and motor effects is discussed.

Criteria for Assessing the Level of Group Development (LGD) of Work Groups Groupness, Entitativity, and Groupality as Theoretical Perspectives

The main objective of this study is to identify criteria that would allow us to determine when a collection of people is a group. A bibliographic search of the psychological literature has yielded the terms groupness, entitativity, and groupality. These three constructs are then theoretically analyzed and compared, and are found to share two main aspects: (a) the conception of groups as a continuum varying in their level of group development (LGD) and (b) most of the central criteria that have been considered to define a group as a group. Regarding these central criteria, we categorize them as determining elements, LGD criteria, and group results trying to respect their different epistemological positions. The theoretical proposal outlined here provides a basis on which to develop tools that will enrich organizational assessment.

Coadministration of l-NOARG and tiapride: Effects on catalepsy in male mice

This study was designed to determine the possible potentiation of catalepsy behavior after coadministration of N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (NOS), and tiapride, a specific antagonist for D2 receptors, in male mice. Catalepsy was measured by the bar test. Two successive evaluations were carried out 60 and 90 min after injections. The induction of catalepsy following coadministration of L-NOARG (25 and 50 mg/kg) and tiapride (200 mg/kg) was significantly higher than the sum of catalepsy scores after administration of L-NOARG and tiapride separately. Coadministration of L-NOARG and tiapride produced a clear potentiation of their effects on catalepsy in mice. These results underline the view that nitric oxide (NO) interacts with central dopamine D2 transmission.

Effects of morphine hydrochloride on social encounters between male mice

The effects of a single injection of morphine hydrochloride (0.3, 0.6, or 1.25 mg/kg) or physiological saline (0.9% NaCI) on the agonistic behaviour elicited by isolation in male mice were examined. Individually housed mice were exposed to anosmic “standard opponents” 30 minutes after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. Morphine (at 0.6 and 1.25 mg/kg) significantly and dose-dependently decreased time spent in offensive (“threat” and “attack”) and “digging” behaviours but markedly increased “non-social exploration” without a significant increase of “immobility.” The lowest dose was completely ineffective in producing changes in any of the behaviours studied. It is concluded that these results present a specific ethopharmacological profile characterized by suppression of aggressive behaviour, increase in non-social explotation, and no evident impairment of motor activity.

TIAPRIDE-INDUCED CATALEPSY IS POTENTIATED BY GAMMA-HYDROXYBUTYRIC ACID ADMINISTRATION

1. The effect of administration of gammahydroxybutyrate (GHB) and tiapride, either alone or in combination, on catalepsy behavior was examined in male mice. 2. Catalepsy was measured by bar and grid tests. Two successive evaluations were carried out 30 and 60 min after injections. 3. Tiapride (175 and 200 mg/kg) and gammahydroxybutyrate (200 mg/kg) provoked an increase of catalepsy scores, exhibiting different time courses. GHB produced a marked but short lasting catalepsy with a peak of action at 30 min, while tiapride produced a catalepsy state with a peak of action at 60 min. 4. Tiapride-induced catalepsy was potentiated by gammahydroxybutyrate administration at 30 min (bar test) and 60 min (bar and grid tests). 5. These results underlie the view that GHB interacts with central dopamine D2 transmission.

Circadian typology is related to resilience and optimism in healthy adults

The relationships between circadian typology and several aspects related to mental health, such as satisfaction with life, emotional intelligence, perceived well-being and psychopathological symptomatology have been documented. However, their relationships with two psychological strengths such as resilience and optimism have not been examined yet. Therefore, the purpose of the present study was to explore whether circadian typology is related to both measures, taking into consideration the possible influence of sex. A sample of 1922 participants (978 men), aged between 18 and 60 yrs (30.08 ± 10.53) completed the reduced Morningness–Eveningness Questionnaire (rMEQ), the 10-item Connor-Davidson Resilience Scale (10-item CD-RISC) and the Life Orientation Test-Revised (LOT-R). Circadian typology was associated with different values in resilience (F(2,1915) = 45.89; p < 0.001;  = 0.046) and optimism (F(2,1915) = 37.74; p < 0.001;  = 0.038), independently of the sex. Morning-type subjects showed the highest resilience and optimism scores while the lowest scores were shown by evening-type, exhibiting the neither-type subjects intermediate scores (p < 0.007, in all cases). These results suggest that evening-type subjects could display less capacity to face adversity and adapt positively, as well as less expectance of the occurrence of positive events compared to neither and morning-type individuals. In addition, these results provide new evidence that might improve our understanding about the relationships between circadian typology and psychological traits and disorders. Although future studies with longitudinal designs are needed, the obtained results emphasize that the evening-type could be a risk factor for the development of psychological problems and mental disorders, whereas the morning-type could be considered as a protective factor.