Biomedical subjects

J Podhorna

Publications and source records attributed to J Podhorna.

12 recordsLinked to original sources

PubMed2005

Performance of male C57BL/6J mice and Wistar rats in the water maze following various schedules of phencyclidine treatment.

In order to establish an animal model of cognitive impairments relevant to schizophrenia, we set out to obtain an optimal treatment protocol with phencyclidine (PCP) that would lead to robust cognitive impairment with minimal PCP-related adverse effects. Effects of various doses (0.63-5 mg/kg), pre-treatment period (0, 3, 7 and 10 days before the beginning of acquisition) and treatment schedules (before the first or immediately after the last trial on each day) of PCP on the performance of male C57BL/6J mice and Wistar rats in the spatial version of the water maze were studied. In mice, a 10-day pre-treatment period was required to prevent PCP-induced motor impairments, whereas a 3-day pre-treatment was sufficient in rats. PCP impaired spatial learning in both rats and mice, if animals were administered PCP prior to the first trial. The optimal dose was 2.5 mg/kg. In contrast, animals given PCP immediately after the daily training sessions performed as well as controls. Thus, PCP impairs spatial learning in the water maze only when present in the organism. It can be concluded that PCP interferes with learning, and perhaps retrieval, but not consolidation of newly acquired information.

Animals↗

PubMed2004

Subchronic phencyclidine treatment impairs performance of C57BL/6 mice in the attentional set-shifting task.

Schizophrenic patients show deficits in their ability to shift attention to new stimuli during attentional set-shifting tasks. An equivalent task has been developed in rodents. This task was used to assess effects of phencyclidine (PCP), a drug widely used to model schizophrenia, in mice. Mice were administered PCP (0.63 or 1.3 mg/kg) daily, beginning 5 days prior to training and continuing throughout the test period. Mice were trained to discriminate stimuli to find a food reward in a series of discriminations. PCP increased the number of trials required to reach the criterion during simple and reversal discriminations, but not when the discriminations were repeated with a new set of stimuli (i.e. during the intradimensional shift and its reversal), suggesting an interaction between PCP effects and novelty. The 1.3 mg/kg of PCP also impaired performance of mice during the extradimensional shift. Similar results have been reported in schizophrenic patients. Although, in control mice, performance of the extradimensional shift was not impaired relative to the intradimensional shift, suggesting that the mouse may not be a suitable species for assessment in this model, specific discriminations within this task were sensitive to impairment by PCP, implying, therefore, that it may have some utility in modelling discrete aspects of schizophrenia in humans.

Animals↗

PubMed2002

Male and female C57BL/6 mice respond differently to diazepam challenge in avoidance learning tasks.

Benzodiazepines (BZ) impair learning and memory performance of animals. The goal of this study was to examine sex differences in the effects of diazepam on learning and memory of C57BL/6 mice in avoidance paradigms. Male and female C57BL/6 mice were tested in the one-way active avoidance, step-down passive avoidance, and foot-shock pain threshold tasks, following administration of vehicle or diazepam (1 mg/kg). No substantial sex or drug effects on the threshold of the pain response to shock were found. There were no significant differences in avoidance performance between vehicle-treated male and female mice while 1 mg/kg of diazepam produced opposite effects on performance of males and females in both tasks. Diazepam-treated females learned faster in the active avoidance task and showed stronger retention in the passive avoidance task. In contrast, diazepam impaired learning of males in the active avoidance task and had no effect on their performance in the passive avoidance task. Diazepam-induced impairment in males was not due to higher sensitivity to the sedative effect of diazepam as females were more sedated than males on the first trial of the passive avoidance task. Our data showed that sedative and amnesic effects of BZs are not tightly linked. This study also suggests that cognitive effects of BZs in rodents could be sex dependent and highlight the importance of using both sexes in studies on behavioral effects of psychoactive drugs.

Animals↗

PubMed2002

Strain differences in activity and emotionality do not account for differences in learning and memory performance between C57BL/6 and DBA/2 mice.

This study examined emotionality, activity, learning and memory, as well as the influence of emotionality and activity on learning and memory performance in C57BL/6 and DBA/2 mice using a mouse-test battery. DBA/2 mice performed more poorly than C57BL/6 mice in complex learning tasks such as the water maze and object recognition tasks. In contrast, C57BL/ 6 mice showed attenuated habituation tonovelty in the open field apparatus and poorer performance in the step-down passive avoidance task. The C57BL/6 mice were less exploratory and more anxious than the DBA/ 2 mice. The anxiety score (open arm entries in the elevated plus maze) was significantly correlated with all measures of learning and memory in the object recognition task, and some measures in the passive avoidance and water maze tasks. Analysis of covariance (with open arm entries as a covariate) revealed that some measures on trial 1 of the object recognition task, but not the memory scores on trial 2,were confounded by anxiety. No confounding factors of anxiety were found in the water maze or passive avoidance tasks. Similar results were obtained with the activity scores (line crossing and rearing in the open field). In conclusion, strain differences in activity and anxiety did not account for strain differences in learning and memory performance of C57BL/6 and DBA/2 mice. Nonetheless, the importance of using complete behavioural test batteries should be stressed to ensure that strain differences in learning and memory tasks are not confounded by non-cognitive factors.

Animals↗

PubMed2002

The experimental pharmacotherapy of benzodiazepine withdrawal.

In many people, long-term benzodiazepine (BZ) use produces dependence with manifestation of withdrawal symptoms after abrupt cessation of BZ treatment. The current therapy of BZ dependence in humans utilizes gradual dose-taper to avoid withdrawal symptoms and supportive psychotherapy to help patients cope with withdrawal reactions. The failure of dose-taper in many patients has triggered intensive animal research to find additional pharmacological treatments. The present article reviews evidence from animal studies on effectiveness of pharmacological treatment for BZ dependence and withdrawal. It explores the risk-benefit profiles of putative therapies for BZ withdrawal, including drugs acting via benzodiazepine receptors, serotonergic and noradrenergic agents, cholecystokinin-B receptor antagonists, calcium channel blockers, N-methyl-D-aspartate (NMDA) antagonists, and other miscellaneous agents.

Animals↗

PubMed2000

Interactions between N-methyl-D-aspartate and nitric oxide in the modulation of ultrasonic vocalizations of infant rats.

The effects of interactions between N-methyl-D-aspartate (NMDA) and nitric oxide on ultrasonic vocalizations, motor activity and body temperature was investigated in 9-10-day-old rat pups. The competitive NMDA receptor antagonist, 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), and the nitric oxide synthase inhibitor, nitro-L-arginine-methyl ester (L-NAME), decreased the emission of ultrasonic vocalizations while NMDA and the nitric oxide precursor, L-arginine, produced a trend toward increased emission of ultrasonic vocalizations. CCP also attenuated the geotaxic response. Co-administration of CPP with L-NAME virtually abolished the emission of ultrasonic vocalizations and the ability to show the geotaxic response while co-administration of NMDA with L-arginine increased the emission of ultrasonic vocalizations and decreased body temperature with no effect on the geotaxic response. NMDA and L-arginine reversed the effects of L-NAME, but not of CPP, on ultrasonic vocalizations. L-arginine but not NMDA antagonized the effect of CPP on the geotaxic response. Our results confirmed the functional coupling between NMDA receptor activation and nitric oxide in modulating anxiety-like behavior and motor coordination in infant rats.

Animals↗

PubMed2000

Pontine tegmentum lesions increase anxiety-like behavior in rats: a comparison with anxiety produced by beta-CCE.

Electrolytic lesions of the pedunculopontine tegmental nucleus (PPTg) have been previously reported to increase anxiety-like behavior in rats. The aim of the present study was to compare these behavioral changes with those produced by an anxiogenic compound, the partial inverse agonist at benzodiazepine receptors, beta-CCE. Three groups of rats, sham-lesioned treated with vehicle, sham-lesioned treated with 10 mg/kg of beta-CCE, and PPTg-lesioned rats treated with vehicle, were tested in the elevated plus-maze, the social-interaction test, and for spontaneous locomotion. Histology showed that lesions were concentrated on the caudal half of the PPTg. Measures of both the PPTg-lesioned and beta-CCE-treated rats indicated increased anxiety-like behavior in the elevated plus-maze and in the social-interaction test. Spontaneous locomotion, measured in the open- field arena, did not differ between sham controls and PPTg-lesioned rats, but was decreased in rats treated with beta-CCE. Our results confirmed that electrolytic lesions of the caudal PPTg produce increased anxiety-like behavior. This behavior is quantitatively and qualitatively similar to that produced by 10 mg/kg of beta-CCE.

Animals↗

PubMed2000

Flibanserin has anxiolytic effects without locomotor side effects in the infant rat ultrasonic vocalization model of anxiety.

This study compared the effects of flibanserin, a novel 5-HT(1A) agonist/5-HT(2A) antagonist; diazepam, a traditional anxiolytic; and imipramine, a traditional antidepressant, on separation-induced ultrasonic vocalizations (USVs), locomotor behaviour, negative geotaxis and body temperature of 7 - 8-day-old rat pups. Flibanserin (5, 10, 25 and 50 mg kg(-1) s.c.) reduced USVs but had no effects on locomotor behaviour or negative geotaxis. Lower doses of flibanserin (0.5, 1, 2 and 4 mg kg(-1) s.c.) had no effect on any behaviour. Diazepam (0.25, 0.5, 1 and 2 mg kg(-1) s.c.) not only reduced the USVs but also increased rolling and increased the latency of the negative geotaxic response. Imipramine (10, 15, 20 and 30 mg kg(-1) s.c.) reduced USVs, increased total locomotor activity and rolling but had no effect on negative geotaxis. None of the drugs altered body temperature. Our data showed that flibanserin is as effective in reducing the USVs as diazepam and imipramine but has a lower incidence of motor side effects. This suggests that flibanserin might be effective for the treatment of mood disturbances such as anxiety.

Animals↗

PubMed2000

Behavioural effects of a benzodiazepine receptor partial agonist, Ro 19-8022, in the social conflict test in mice.

The study examined the effects of the benzodiazepine receptor partial agonist, Ro 19-8022, on anxiety-like, aggressive, social and locomotor behaviours in timid ('anxious') and aggressive mice in the social conflict test. To test the hypothesis that Ro 19-8022 acts as a partial agonist in this model, i.e. it reduces anxiety-like and aggressive behaviours without affecting motor coordination, its effects were compared to those of the full agonist, nitrazepam. Both Ro 19-8022 and nitrazepam decreased anxiety-like behaviour in timid mice and aggressive behaviour in aggressive mice. The effect of the full agonist, nitrazepam, was dose-dependent while the effect of the partial agonist, Ro 19-8022, was lower in magnitude and reflected its partial agonistic properties. Both drugs stimulated social behaviour in both groups of mice, presumably due to disinhibition of anxiety or aggression. The marked difference was in their effects on motor coordination, as nitrazepam, but not Ro 19-8022, produced motor impairment at higher doses. Thus, Ro 19-8022 produces anxiolytic-like and potent anti-aggressive effects without causing muscle relaxation or ataxia in the present model. Our data confirm that the main behavioural differences between partial and full benzodiazepine receptor agonists are in their side-effect profiles.

Aggression↗

PubMed1999

Inhibition of nitric oxide synthase reduces ultrasonic vocalizations of rat pups.

The present study investigated the effects of drugs acting on the brain nitric oxide pathway on ultrasonic vocalizations, body temperature and locomotion in 7-8-day-old rat pups. Both a selective neuronal nitric oxide synthase (NOS) inhibitor (7-nitroindazole) and a non-selective NOS inhibitor (nitro-L-arginine-methyl ester, L-NAME) decreased the number of ultrasonic vocalizations in a dose-dependent manner. The non-selective NOS inhibitor, L-NAME, suppressed not only ultrasonic vocalizations but also locomotion. The inactive isomer of the NOS inhibitor, nitro-D-arginine-methyl ester (D-NAME), and the biological precursor of nitric oxide, L-arginine, had no effect on ultrasonic vocalizations or locomotion. These data indicate that drugs suppressing nitric oxide synthesis produced an anxiolytic effect in rat pups. However, only the selective NOS inhibitor, 7-nitroindazole, was 'anxioselective', i.e., reduced ultrasonic vocalizations without causing sedation. Increased synthesis of nitric oxide in the brain had no apparent behavioral effect in this model.

Animals↗

PubMed1999

Long-lasting increase in anxiety after electrolytic lesions of the pedunculopontine tegmental nucleus.

This study examined the effect of electrolytic lesions of the pedunculopontine tegmental nucleus (PPTg) on emotionality in rats. Rats with PPTg or sham lesions were tested in the elevated plus-maze, the social interaction test, the open-field test, and the conditioned fear paradigm. Histology showed that lesions were concentrated on the caudal half of the PPTg. In the plus-maze, behavioral scores were biased toward increased "anxiety" on the 1st testing day. Five consecutive exposures to the apparatus led to marked habituation in sham-lesioned but not in PPTg-lesioned rats. On the 5th day, most indexes of emotionality indicated elevated anxiety in PPTg-lesioned rats. Increased anxiety was also found in PPTg-lesioned rats in the social interaction test. In the conditioned fear paradigm, movement suppression during the postconditioned stimulus period was found in both groups on the 1st day of extinction but only in PPTg-lesioned rats on the 2nd extinction day, indicating extinction was slower in PPTg-lesioned rats. Lesions of the caudal PPTg appear to produce long-lasting anxiety in rats.

Animals↗

PubMed1998

Lesions of the pedunclopontine tegmental nucleus increase anxiety in rats.

To test the hypothesis that the pedunclopontine tegmental nucleus (PPTg) plays a role in anxiety, rats with electrolytic lesions of the PPTg were tested in two animal models of anxiety, the elevated plus maze and the social interaction tests. Histological analysis showed that lesions were concentrated on the caudal half of the PPTg. In the elevated plus maze, traditional as well as 'risk assessment' measures indicated significantly increased anxiety in the PPTg-lesioned rats vs sham-operated controls. In the social interaction test, behavioural scores were biased towards elevated anxiety in the PPTg-lesioned rats but only the number of social sniffs reached significance. Our results confirm that electrolytic lesions of the caudal PPTg produce increased anxiety.

Animals↗