Effects of promazine, chlorpromazine, d-amphetamine, and pentobarbital on treadle pressing by pigeons under a signalled shock-postponement schedule.
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The effects of promazine on treadle pressing to postpone the presentation of electric shock were studied in three pigeons. The effects of chlorpromazine, d-amphetamine, and pentobarbital were studied in two of these pigeons. Each treadle press postponed electric shock for 20 sec and presentation of a preshock stimulus for 14 sec. Selected doses of both promazine and chlorpromazine increased the rates of treadle pressing in all birds. The response-rate increases produced by promazine and chlorpromazine were due to increased conditional probabilities of treadle pressing both before and during the preshock stimulus. d-Amphetamine (1 and 3 mg/kg) slightly increased responding in one of the birds, but not to the extent that promazine or chlorpromazine did. In the other bird, the 10 mg/kg dose of d-amphetamine increased shock rate but did not change response rate. Some doses of d-amphetamine increased the conditional probabilities of responding both in the absence of the preshock signal and during the preshock signal in both birds. Pentobarbital only decreased response rates and increased shock rates. (+info)
The effects of d-amphetamine on the temporal control of operant responding in rats during a preshock stimulus.
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The operant behavior of six rats was maintained by a random-interval schedule of reinforcement. Three-minute periods of noise were superimposed on this behavior, each period ending with the delivery of an unavoidable shock. Overall rates of responding were generally lower during the periods of noise than in its absence (conditioned suppression). These suppressed response rates also exhibited temporal patterning, with responding becoming less frequent as each noise period progressed. The effects of d-amphetamine on this behavioral baseline were then assessed. In four animals the relative response rates during the noise and in its absence suggested that the drug produced a dose-related decrease in the amount of conditioned suppression. However, this effect was often due to a decrease in the rates of responding in the absence of the preshock stimulus, rather than to an increase in response rates during the stimulus. Temporal patterning in response rates during the preshock stimulus was abolished, an effect that was interpreted in terms of rate-dependent effect of d-amphetamine. This study thus extends rate-dependent analyses of the effects of amphetamines to the patterns of operant behavior that occur during a preshock stimulus, and which have been discussed in terms of the disrupting effects of anxiety on operant behavior. (+info)
Determination of the lipophilicity of active anticonvulsant N-substituted amides of alpha-arylalkylamine-gamma-hydroxybutyric acid.
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The lipophilicities of fourteen anticonvulsant active N-substituted amides of alpha-arylalkylamine-gamma-hydroxybutyric acid [I-XIV] have been determined by reversed-phase thin-layer chromatography with a mixture of methanol, TRIS buffer, and acetic acid as the solvent system. The RM value of each compound decreased linearly with increasing concentration of methanol. The partition coefficients (log P) of the amides were calculated by use of the Prolog P module of the Pallas system. Comparison of RM and log P enabled clog P values to be calculated. It was found that the anticonvulsant activity of amides [I-XIV] can be explained on the basis of their lipophilicity. (+info)
Characterization of socio-psychological stress-induced antinociception in the formalin test in mice.
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The antinociceptive effect induced by exposure to socio-psychological (PSY) stress using a communication box was assessed by the formalin test in mice, compared with those by exposure to footshock (FS) stress and forced swimming (SW) stress. After the termination of stress exposure, whereas exposure to FS- and SW-stress resulted in the attenuation of the formalin-induced biphasic pain response over 15 min, no appreciable antinociceptive effect was found in the case of PSY stress. When exposure to PSY stress was started during the period of early or late phase of pain after the formalin injection, the antinociceptive effect was maintained for 5-15 min; however, further exposure to PSY stress was not effective for producing antinociception. In the tail-pinch test, likewise, exposure to PSY stress longer than 5 min rather decreased the intensity of antinociception. We conclude that PSY stress in this tonic pain paradigm produces antinociception, but further continuous exposure to the emotional stress caused mice to become recuperative even in such a fear-inducing situation. (+info)
Rat strain differences in the acquisition of conditioned avoidance responses and in the effects of diazepam.
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Adult male albino rats of three strains--Wistar, Sprague-Dawley and Holtzman--were trained to press a lever to avoid electric shocks under Sidman-type (R-S interval-20 sec; S-S interval=5 sec) and discriminated avoidance (ITI-15 sec; warning duration=5 sec) schedules, and the acquisition processes of avoidance responses, and the properties of behavioral baselines were investigated. Under both schedules, Wistar strain rats, though showing poorer results than the other two in the beginning, rapidly progressed with the repetitive training, and finally displayed excellent and stable performances. Srague-Dawley strain rats were poorer in performances, with delayed acquisition and prolonged warm-up effect in the within-session performance. The results of Holtzman strain rats ranked between the two. After the establishment of stable behavioral baselines under both schedules, 0.5, 1.0 and 2.0 mg/kg of diazepam were given subcutaneously, and it was found that in Wistar and Holtzman strain rats, the avoidance responses were inhibited together with increase of delivered shocks in parallel to the doses. In Sprague-Dawley strain rats, however, the avoidance responses were conversely improved with 0.5 and 1.0 mg/kg, while such tended to be inhibited with 2.0 mg/kg, with marked concomitant ataxia. As definite strain differences in avoidance response were demonstrated herein, selection of the most appropriate strain should be made when designing behavioral experiments. (+info)
Effects of age on the generalization and incubation of memory in the F344 rat.
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Freezing (immobility) in the presence of aversive stimuli is a species-specific behavior that is used as an operational measure of fear. Conditioning of this response to discrete sensory stimuli and environmental context cues has been used as a tool to study the neuropsychology of memory dynamics and their development over the lifespan. Three age groups of F344 rats (3, 9, and 27 month) received tone-foot shock pairing (or tone only) in a distinctive chamber on two consecutive days. Separate subgroups of rats from each age group were then tested, at retention intervals of 1, 20, 40, or 60 days, for context-mediated fear in the environment in which they were trained, for generalization of the fear response to a novel chamber, and for fear of the tone. Beginning at day 20, the 27-month-old rats exhibited less freezing behavior than did younger rats when tested in the conditioning context. This age difference was a result of freezing behavior becoming progressively stronger with time in the two younger age groups, a phenomenon that has been referred to as memory incubation. Incubation of the contextual fear response was not detected in the old rats. In a novel context, all age groups exhibited significantly more freezing than did control animals. There was also pronounced incubation of this generalized freezing response, and the extent of incubation declined significantly with age. In the novel context, the freezing response to the tone was robust in all age groups and increased over time, in constant proportion to the degree of freezing elicited by the novel context itself, prior to tone onset. The fact that old animals are known to be relatively selectively impaired in forms of memory that depend on a functional hippocampus suggests a possible explanation for the reduced incubation effects seen in old rats; however, whether the increased expression of fear over time is mediated by a hippocampal-dependent memory consolidation process or whether it reflects a generalized increase in the gain of the circuitry mediating the fear response itself, remains to be determined. (+info)
Effects of exposure conditions to footshocks early in life on spontaneous locomotor activity at maturity in rats.
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Both genetic and environmental factors are involved in establishing a behavior. An animal study was done to determine the characteristics of interaction between genetic (nature) and environmental (nurture) factors. Delivery of footshocks (0.8 mA x 60 times, at random) early in life was used as the environmental stimulus. As the footshock was delivered repeatedly, a rat showed helplessness behavior and the number of shocks necessary to elicit helplessness was measured to quantify the trait of an animal in coping with the aversive environmental stimulus. The nocturnal ambulatory activity at adulthood was measured as a behavioral expression of the nature-nurture interaction. Although the experience of footshocks early in life did not significantly alter average activity levels at adulthood, the activity was positively correlated with the number of shocks necessary to elicit helplessness (nature) while receiving footshocks (nurture) on postnatal day 14. Additionally, a second exposure to identical shock parameters on postnatal day 21 reversed the relationship. These results clearly showed that an interaction between nature and nurture during infancy leads to substantial behavioral alterations later in life, and suggest that the nature-dependent determination of an adult behavior can be modified in different directions by the conditions of an environmental experience early in life. (+info)
BIIR 561 CL: a novel combined antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and voltage-dependent sodium channels with anticonvulsive and neuroprotective properties.
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Antagonists of glutamate receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype, as well as of voltage-gated sodium channels, exhibit anticonvulsive and neuroprotective properties in vivo. One can postulate that a compound that combines both principles might be useful for the treatment of disorders of the central nervous system, like focal or global ischemia. Here, we present data on the effects of dimethyl-(2-[2-(3-phenyl-[1,2, 4]oxadiazol-5-yl)-phenoxy]ethyl)-amine hydrochloride (BIIR 561 CL) on neuronal AMPA receptors and voltage-dependent sodium channels. BIIR 561 CL inhibited AMPA receptor-mediated membrane currents in cultured cortical neurons with an IC50 value of 8.5 microM. The inhibition was noncompetitive. In a cortical wedge preparation, BIIR 561 CL reduced AMPA-induced depolarizations with an IC50 value of 10.8 microM. In addition to the effects on the glutamatergic system, BIIR 561 CL inhibited binding of radiolabeled batrachotoxin to rat brain synaptosomal membranes with a Ki value of 1.2 microM. The compound reduced sodium currents in voltage-clamped cortical neurons with an IC50 value of 5.2 microM and inhibited the veratridine-induced release of glutamate from rat brain slices with an IC50 value of 2.3 microM. Thus, BIIR 561 CL inhibited AMPA receptors and voltage-gated sodium channels in a variety of preparations. BIIR 561 CL suppressed tonic seizures in a maximum electroshock model in mice with an ED50 value of 2.8 mg/kg after s.c. administration. In a model of focal ischemia in mice, i.p. administration of 6 or 60 mg/kg BIIR 561 CL reduced the area of the infarcted cortical surface. These data show that BIIR 561 CL is a combined antagonist of AMPA receptors and voltage-gated sodium channels with promising anticonvulsive and neuroprotective properties. (+info)