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The neuroanatomical specificity of the anxiolytic effects of intra-septal infusions of midazolam.

Microinfusions of the benzodiazepine anxiolytic midazolam into the lateral but not the medial septum suppressed fear reactions in two test of rat 'anxiety'. Midazolam infusions into the lateral septal nuclei increased open-arm exploration in the elevated plus-maze test, and blocked burying behavior in the shock-probe test, whereas midazolam infusions into the medial septum produced neither of these anxiolytic effects. The anxiolytic effects of midazolam in the lateral septum were partially blocked by pre-infusion of the benzodiazepine receptor antagonist Ro15-1788, which had no intrinsic effects by itself. These results suggest that the anxiolytic effects of intra-septal midazolam occur, at least in part, at GABAA-benzodiazepine receptor sites located in the lateral septal nuclei.

Animals↗

The effects of antidepressants and electroconvulsive shocks on the functioning of the mesolimbic dopaminergic system: a behavioral study.

The mesolimbic dopaminergic innervation is supposed to be involved in the mechanisms of central effects exerted by various classes of psychotropic drugs. Antidepressants have been found to interact with the brain dopaminergic system as well, although the precise central location of this interaction is unknown. Some data point to the mesolimbic dopaminergic system as a possible target for antidepressant action. The aim of the present experiment was to verify this hypothesis. It was found that a long-term treatment of rats with desipramine, citalopram or electroconvulsive shocks potentiated the dopaminergic mechanisms within the nucleus accumbens, as evidenced by an increase in or the appearance of behavioral effects (exploratory locomotion, an active behavior in the Porsolt test) following microinjections of dopaminergic agonists into this brain area. Similar results obtained with different methods of treatment for depression indicate that the effect of antidepressants and electroshocks on dopaminergic mechanisms within the nucleus accumbens may be linked directly to the mechanism of their antidepressant action.

Animals↗

Effects of 5-HT1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze.

The effects of several 5-HT1A agonists and excitatory amino acid antagonists were compared to the standard benzodiazepines, diazepam and chlordiazepoxide (CDP) in two assays predictive of anxiolytic activity, the social interaction and elevated plus maze procedures. Indicative of anxiolytic effects the 5-HT1A agonists, buspirone, gepirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) all significantly increased social interaction time and open arm exploration time in the social interaction and elevated plus maze procedures, respectively. Likewise, anxiolytic activity in these assays were also produced by the competitive N-methyl-D-aspartate (NMDA) antagonists, 2-amino-5-phosphonovaleric acid (AP-5), 2-amino-7-phosphonoheptanoic acid (AP-7), 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the non-competitive NMDA antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) while NMDA produced anxiogenic effects. Furthermore, the anxiolytic effects of these agents were of equal magnitude to the benzodiazepines. These two classes of compounds were differentiated in the yohimbine-induced seizure assay, with the NMDA antagonists dose dependently antagonizing seizures similar to the benzodiazepines while the 5-HT1A agonists were inactive. These results suggest that the 5-HT1A agonists and the NMDA antagonists may be potential non-classical anxiolytic agents with different mechanisms of action.

Animals↗

Mediation of dopamine D1 and D2 receptors in the effects of GBR 12909 on latent learning and locomotor activity in mice.

We investigated the involvement of dopamine D1 and D2 receptor subtypes in the effects of GBR 12909, a selective dopamine uptake inhibitor, on latent learning in the performance of a water-finding task and on locomotor activity in mice. GBR 12909 (10 and 20 mg/kg) impaired latent learning, and this effect was counteracted by the dopamine D2 receptor antagonist, (-)-sulpiride (20 and 40 mg/kg), but not by the dopamine D1 receptor antagonist, SCH 23390 (0.025 and 0.05 mg/kg). The dopamine D2 receptor agonist, quinpirole (0.5 and 1 mg/kg) and the dopamine D1 receptor agonist, SKF 38393 (20 mg/kg) impaired latent learning, but both effects were less than that of GBR-12909. The effect of quinpirole, but not of GBR 12909, on latent learning was potentiated by combination with SKF 38393. In contrast to its effect on learning, SCH 23390 (0.025 and 0.05 mg/kg) was more effective to suppress the stimulant effect of GBR 12909 on locomotor activity than was (-)-sulpiride (40 and 80 mg/kg). These findings suggest that both dopamine D1 and D2 receptors play an important role in the action of endogenously released dopamine in latent learning and locomotor activity, and that while the dopamine D2 receptor is involved predominantly in latent learning, both dopamine D1 and D2 receptors play a critical role in locomotor activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Effects of enucleation in retinal degenerate mice.

Two experiments are reported which examine the effects of optic enucleation upon behavior of retinal degenerate C3H/HeJ mice. Enucleation did not affect acquisition of a two-way avoidance task. However, enucleated mice were more active than unoperated controls. The increased activity was not specific to the avoidance task since it also occurred in the closed field. The enucleation-induced increase in closed field activity did not depend upon age at time of testing or postsurgical recovery time. Several alternative explanations are considered, including the possibility that some information may be processed by the eye in the absence of traditionally conceived photoreceptors.

Animals↗

Altered responsiveness to ambiental stimuli in altered thyroidal states.

Hypothyroidal rats produced by low iodine diet or propylthiouracyl (PTU) were less active in the open field and received fewer food reinforcements than controls in a lever press situation at both 22 degrees C and 1 degree C. The hypothyroid rats also pressed less when heat was the reinforcer. On the other hand, hyperthyroidal rats produced by thyroid powder ingestion showed reduced emotionality in the open field. Acute exposure to cold failed to increase their alimentary or heat reinforced behavior. The results suggest that hypothyroidism produces a general inattention to the environment. This is found whether the environmental stimulus is an opportunity to explore, access to food or the availability of external heat.

Animals↗

The influence of prenatal and/or postnatal exposure to lead on behavior of preweanling mice.

Binghamton Heterogeneous (HET) Stock mice received prenatal exposure to either water or a 0.5% lead acetate solution via their biological dam. At birth, litters were cross-fostered so that they were postnatally exposed to either water or lead via their foster dam. Early preweaning measures of square crossing and standups in an open field and time to return to home cage nest showed that the effects of lead on behavior depend on: the developmental stage(s) during which the individual is exposed to the toxin, as well as age and conditions when tested.

Age Factors↗

The use of CXB recombinant inbred mice to detect quantitative trait loci in behavior.

Although recombinant inbred (RI) series of mice have been developed to identify and map single-gene characteristics, they can also be used to identify quantitative trait loci (QTL) that account for small amounts of variance in quantitative traits such as behavior. We applied an RI QTL approach to the analysis of published behavioral data from seven studies that used the CXB RI series of mice. Nearly all of the behaviors showed strain distribution patterns indicative of multiple-gene rather than single-gene influence. Although the CXB series is limited to seven RI strains, RI QTL association analysis suggests QTL candidate markers for several behaviors, including avoidance and exploration.

Animals↗

Ethological categorization of adult rat motor behavior in an open field.

From 100 rats observed during 1 h, elementary behavioral units were identified, characterized, and behavioral boundaries were established. From this, two main categories were established and named a) basic body postures, and b) posture-associated moving actions. Four subcategories concerning posture-associated moving actions were 1) body-directed actions; 2) actions of interaction with the environment; 3) moving actions without locomotion; and 4) displacement actions with locomotion. This ethological characterization in an open field could be applied to the study of motor effect induced by experimental manipulation of the brain function, at maturity.

Animals↗

Behavioral consequences of predictable vs. unpredictable shocks in rats.

Adult, male, Sprague-Dawley rats were given either predictable or unpredictable footshocks coupled with predictable or unpredictable warning stimuli in a factorially designed experiment. The effect of footshocks on different parameters of motility was studied immediately, 1 h and 24 h later. Footshock-induced stress caused increases in the motility of rats, and this increase persisted for 24 h. Of the parameters studied, distance travelled and time spent in ambulatory behavior were significantly affected, but there was no difference between the predictably and unpredictably shocked animals in the pattern or time course of stress-induced locomotion changes. The defecation scores recorded in footshocked rats were lower than in controls in both the predictably and unpredictably shocked groups, but there was no difference between the predictably and unpredictably shocked groups. Lack of differences in motility and defecation between the two groups limits the usefulness of these parameters in behavioral experiments based on predictability of noxious stimuli.

Animals↗

Effect of early experience on behavior and immune response in the rat.

The effect of maternal deprivation (MD) and preweaning handling on open field (OF) behavior, body and organ weights (spleen, thymus, and adrenals), and humoral immune response (plaque-forming cell response and antibody production) in adult male and female Wistar rats was studied. Maternal deprivation took place either for 28 postnatal days (2 h/day), or on days 15, 18, and 21 (2 h/day), whereas handling was performed daily during 28 postnatal days for 3 min. Sex differences were found both in behavior and immune response. The MD rats showed ambulatory hyperactivity in OF tests, females being more active than males, and a marked suppression of the PFC response. Handled rat's behavior was distinguishable from MD rats by an increased curiosity. Female handled rats were more active in the OF and their antibody production was higher. Male handled rats showed higher defecation scores and lower plaque-forming cell response. These results present evidence for a deprivation syndrome and immunosuppressive behavior in MD rats. Several mechanisms that may account for these immunobehavioral results are outlined.

Animals↗

Individual behavioral and physiological strategies in pigs.

Previous experiments demonstrated consistent individual behavioral differences in pigs. Some showed a more active behavioral response (so-called A/R pigs), others a more passive behavioral response (so-called NA/NR pigs). In the present study we selected 32 A/R and 32 NA/NR individuals and tested them individually in an open field at 3 (OF1) and 8 weeks of age (OF2). Individual response patterns were remarkably consistent between OF1 and OF2. While more A/R than NA/NR pigs made escape attempts, the A/R ones vocalized less, and were less inhibited to approach novel objects in OF1 and OF2, although they spent less time in exploring these objects than NA/NR pigs. Cortisol (CS) level after OF1 increased in A/R pigs but did not change in NA/NR ones, while CS level in OF2 remained constant in A/R pigs but decreased in NA/NR pigs. CS response to ACTH1-39 was measured at 3 and 8 weeks of age but did not differ between types. Basal CS level was higher in NA/NR than in A/R pigs and accompanied by adrenal hypertrophy. Mean heart rate (HR) was higher of A/R pigs compared to NA/NR ones in two backtests. HR of A/R pigs substantially increased (23.9 bpm = 15.5%) in reaction to the novel object in OF2, while HR of NA/NR ones only slightly increased (4.5 bpm = 2.9%), or even decreased (bradycardia). A/R pigs had more often heart deviations than NA/NR ones. The present study demonstrates that the two behavioral strategies of pigs are characterized by consistent differences in behavioral, physiological, and endocrine responses to conflict situations.

Adaptation, Psychological↗