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S Cabib

Publications and source records attributed to S Cabib.

At least 73 records · Page 4Linked to original sources

Repeated stressful experiences differently affect brain dopamine receptor subtypes.

The binding of tritiated spiperone (D2 antagonist) and tritiated SCH 23390 (D1 antagonist), in vivo, was investigated in the caudatus putamen (CP) and nucleus accumbens septi (NAS) of mice submitted to ten daily restraint stress sessions. Mice sacrificed 24 hr after the last stressful experience presented a 64% decrease of D2 receptor density (Bmax) but no changes in D1 receptor density in the NAS. In the CP a much smaller (11%) reduction of D2 receptor density was accompanied by a 10% increase of D1 receptors. These results show that the two types of dopamine (DA) receptors adapt in different or even opposite ways to environmental pressure, leading to imbalance between them.

Animals↗

Post-training dopamine receptor agonists and antagonists affect memory storage in mice irrespective of their selectivity for D1 or D2 receptors.

Post-training administration of the selective D1 and D2 agonists SKF 38393 and LY 171555 dose-dependently facilitated retention of an inhibitory avoidance response in mice, while the selective D1 or D2 antagonists SCH 23390 and (-)sulpiride produced an impairment of retention. These effects are not to be ascribed to a nonspecific action of the drugs on retention performance, as the latencies during the retention test of those mice that had not received a footshock during the training were not increased by the post-training drug administration. The effects on retention performance induced by DA agonists and antagonists seem to be due to an effect on memory consolidation, since they have been observed when drugs were given at short, but not at long, periods of time after training. These results showing a similar role of D1 and D2 receptor types on memory storage appear not to be consistent with a body of neuropharmacological, neurophysiological, and behavioral evidence pointing to a different functional role of these types of DA receptors. This discrepancy is discussed in terms of possible involvement of different brain systems, peripheral systems, or possible second messenger processes activated by the two receptor types and leading to similar effects on memory processes.

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

Strain-dependent differences in hippocampal glucocorticoid binding capacity and active avoidance in the mouse.

Maximal individual [3H]corticosterone binding capacity in the hippocampus was lower in C57BL/6 mice than in BALB/c mice, and positively correlated with active avoidance learning in the two strains. Moreover, a parallel difference in the activity of hypothalamo-pituitary adrenocortical axis (HPAA) was found, consisting in a level of plasma corticosterone in C57BL/6 higher than in BALB/c mice. These results confirm the genetically determined differences in behavior of C57BL/6 and BALB/c mice, and demonstrate their association with differences in hippocampal corticosterone binding capacity, pointing to a functional relationship between the behavioral and neuroendocrine parameters.

Animals↗

Behavioral and biochemical changes monitored in two inbred strains of mice during exploration of an unfamiliar environment.

Mice of the C57BL/6 (C57) and DBA/2 (DBA) strains were introduced individually in an unfamiliar environment (a large cage where food, water and sawdust had been removed). Over a 90-min period of observation, both strains presented a time-dependent decrease of locomotion and leaning and an increase of grooming. C57 mice were characterized by more cage cover climbing than DBA mice during the first 15-min stay in the new cage and by a significant decrease of this behavior after 90 min. During the first 60 min in the new environment, the DBA mice were less active than C57 mice, and both strains presented a significant increase of immobility after 90 min of test. After 30 min in the test situation, C57 presented a larger increase of plasma corticosterone levels than DBA mice. The plasma corticosterone levels were back to control values after 60 min of test in mice of the C57 strain and after 90 min in the DBA strain. Finally, both C57 and DBA mice presented a significant increase of homovanillic acid concentrations in the nucleus accumbens, but not in the striatum at 30, 60 and 90 min of testing. These results are discussed in terms of the possible involvement of mesolimbic dopaminergic system in mouse behavioral responses to an unfamiliar environment and of possible habituation to the stressful properties of this experience.

Animals↗

LY 171555-induced catalepsy and defensive behavior in four strains of mice suggest the involvement of different D2 dopamine receptor systems.

The D2 dopamine receptor agonist LY 171555 (0.5 to 5 mg/kg) induces dose-dependent catalepsy in C57BL/6, DBA/2 and BALB/c inbred strains of mice. This effect shows marked strain-dependent differences, since the response of C57BL/6 is significantly lower than those presented by the other two inbred strains at all doses tested. In previous studies we have shown that the D2 agonist at doses ranging from 0.5 to 5 mg/kg induces hyperdefensive responses toward nonaggressive opponents in mice of the C57BL/6 and BALB/c but not of the DBA/2 strain. Here we report that the outbred CD1 mice present both cataleptic and hyperdefensive responses when challenged with LY 171555. Forty-five percent of individuals presenting high defensive response and 11% high cataleptic scores. No correlation was found between catalepsy and hyperdefensiveness in CD1 mice following administration of 1 mg/kg of the D2 agonist. These results suggest that D2 receptor stimulation results in different behavioral responses, possibly mediated by different dopaminergic systems, depending on the genetic make up.

Animals↗

Role of genotype in the adaptation of the brain dopamine system to stress.

Behavioral and biochemical analysis of the effects of stress on brain dopamine (DA) functioning in two inbred strains of mice reveals opposite patterns of adaptation to chronic stress. Chronically stressed mice of the C57BL/6 (C57) strain are characterized by hypersensitive mesolimbic DA autoreceptors and by a dramatic increase of D1/D2 DA receptor ratio (possibly postsynaptic) in the nucleus accumbens septi (NAS) as revealed by in vivo binding of 3H-spiperone and 3H-SCH23390. Chronically stressed DBA/2 (DBA) mice present, on the contrary, hyposensitive DA autoreceptors and no changes in the D1/D2 DA receptors ratio in this brain area. The analysis of the behavioral responses of chronically stressed mice of the C57 strain to the mixed D1/D2 receptor agonist apomorphine, to the selective D2 agonist LY171555 and to the selective D1 agonist SKF 38393 suggest a close relationship between the behavioral alterations produced by chronic stress and the alterations of sensitivity of D2 pre- and postsynaptic receptors in the mesolimbic system. Furthermore, chronically stressed C57 mice present a marked decrease of spontaneous-climbing behavior which is not observed in the mice of the DBA strain and is dependent on the alteration of the biphasic evolution of this behavior during exposure to the test situation which, for these mice, represents a novel environment. Acute exposure to aversive environmental conditions induces a biphasic alteration of DA transmission (initial increase of DA release followed by a decrease under control levels) in the NAS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Psychological↗

Genotype-dependent modulation of LY 171555-induced defensive behavior in the mouse.

The selective D2 dopamine receptor agonist LY 171555 increased defensive behavior dose dependently, decreased social investigation and activity, and increased immobility in mice of the C57BL/6 (C57) strain interacting with non-aggressive mice of the same strain. In the same test situation, DBA/2 (DBA) mice did not present any increase in defensive behavior following injection of the same doses of LY 171555, while exhibiting a marked decrease in activity and increased immobility. Mice of the BALB/c strain were less responsive than C57 mice as far as defensive behavior was concerned, and showed decreased activity and social investigation and increased immobility. These results point to a major genetic role in the modulation of social behavior by D2 receptors.

Aggression↗

Stress-induced decrease of 3-methoxytyramine in the nucleus accumbens of the mouse is prevented by naltrexone pretreatment.

Pretreatment with naltrexone (2.5 and 5 mg/kg) prevented the decrease of 3-methoxytyramine (3-MT)/dopamine (DA) ratio induced by 2 h immobilization stress in the nucleus accumbens (NAS) of the mouse while it did not affect the stress-induced decrease of 3-MT/DA ratio in caudatus putamen (CP). Naltrexone also produced a slight antagonism of homovanillic acid (HVA)/DA ratio increase produced by stress in the frontal cortex (FC). These results point to an involvement of endogenous opioids in the effects of stress on DA metabolism in the mesolimbic system of the mouse.

Animals↗

Effects of immobilization stress on dopamine and its metabolites in different brain areas of the mouse: role of genotype and stress duration.

Immobilization stress induced, in mice of both C57BL/6 (C57) and DBA/2 (DBA) strains, an increase in dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) and homovanillic acid (HVA)/DA ratios and a reduction of 3-methoxytyramine (3-MT)/DA ratio in the caudatus putamen (CP) and nucleus accumbens septi (NAS). These effects were already evident after 30 min stress in the NAS, while in the CP 120 min were needed in order to show the effects of stress. Immobilization did not produce any effects on dopaminergic metabolism in the frontal cortex (FC) of the C57 strain either after 30 or after 120 min stress while in mice of the DBA strain a time-dependent effect of stress on the HVA/DA ratio was evident. When B6D2F1 hybrids were considered, the effects produced by 120 min immobilization in the CP and the NAS paralleled those observed in parental strains, while in the FC 120 min stress induced the same increase of HVA observed in DBA mice, thus suggesting that the pattern of response in the FC that characterizes the DBA strain may be inherited through a dominant pattern of inheritance.

3,4-Dihydroxyphenylacetic Acid↗

Chronic cocaine enhances defensive behaviour in the laboratory mouse: involvement of D2 dopamine receptors.

C57BL/6 male mice injected with a challenge dose (20 mg/kg) of cocaine 72 h after the end of chronic intermittent treatment with the psychostimulant (two daily injections of 20 mg/kg for 10 days) exhibited a clear-cut increase in defensive upright and sideways postures and escape when confronted with a non-drugged conspecific. Treated mice spent 40% of time showing defensive acts over the 5-min testing session. Administration of the selective D2 receptor antagonist (-)-sulpiride (25 mg/kg) before the challenge dose of cocaine completely antagonized the increase in defensive behaviour, while the selective D1 receptor antagonist SCH 23390 (0.25-0.50 mg/kg) did not significantly affect defensive behavioural patterns. These results suggest the involvement of D2 receptors in cocaine-induced hyperdefensiveness. The hypothesis that alteration in D2 receptor functioning produced by chronic cocaine administration may produce hyperdefensiveness possibly due to altered perceptive processes is discussed.

Animals↗

Different effects of acute and chronic stress on two dopamine-mediated behaviors in the mouse.

After two hours of immobilization stress, C57BL/6 mice presented a significant reduction of spontaneous locomotion and a slight reduction of spontaneous climbing. The effect of stress on locomotor activity disappeared after ten daily sessions of immobilization while this chronic treatment increased the effect of stress on spontaneous climbing. Twenty-four hr after the last stressful experience the mice showed an increase of spontaneous locomotion and a decrease of spontaneous climbing in comparison with unstressed mice. Following a single exposure to immobilization stress, an increase of DOPAC/DA and HVA/DA ratios was found in the striatum and in the nucleus accumbens. These effects were still evident following repeated exposure to this stressor but disappeared 24 hr after the last of ten daily stressful experiences. Finally, chronically stressed mice, tested 24 hr after the last stressful experience, showed an increased sensitivity to the inhibitory effects of low doses of apomorphine on climbing behavior and a decreased sensitivity to the inhibitory effects of the same doses of the dopamine agonist on locomotion. These results are discussed in terms of altered sensitivity of different populations of dopamine receptors following chronic stress.

3,4-Dihydroxyphenylacetic Acid↗

The D2 dopamine receptor agonist LY171555 induces catalepsy in the mouse.

The dopamine agonist LY171555 (quinpirole), a specific D2 receptor agonist, induces catalepsy in mice at doses ranging from 0.3 to 10 mg/kg. The effects of an intermediate dose of this compound (1 mg/kg SC) were antagonized by 25 mg/kg of the selective D2 antagonist (-)-sulpiride (IP) injected 20 min before LY171555. SCH 23390, a selective D1 antagonist, administered (0.3 mg/kg IP) 20 min before LY171555 (1 mg/kg) enhanced the cataleptic effects of this compound. Finally, when the D1 dopamine receptor agonist SKF 38393 (20 mg/kg SC) was administered immediately beforehand, the cataleptic effects of 1 mg/kg of LY171555 were markedly reduced. These results suggest that there is a functional interaction between D1 and D2 dopamine receptors in the modulation of catalepsy.

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

A classical genetic analysis of two apomorphine-induced behaviors in the mouse.

Apomorphine (3 mg/kg) produced in C57BL/6 (C57) mice a clear-cut increase in locomotor activity and climbing behavior in comparison with saline, while in DBA/2 (DBA) mice it produced a clear-cut decrease in locomotion and a small reduction in climbing behavior. Genetic analysis involving F1 and F2 hybrids and the backcross populations (F1 X C57; F1 X DBA) indicated that apomorphine-induced locomotion and climbing are inherited through different modes of inheritance. With regard to climbing behavior the mean analysis of apomorphine parameters showed that the additive-dominance model fitted adequately, while this single model did not fit the locomotor activity data for which the best fitting model involved epistatic parameter. Moreover, a zero correlation between the two behaviors in the F2 generation resulted, indicating that no relationship exists between these apomorphine-induced behaviors under our experimental conditions. These results suggest that the horizontal locomotion and climbing are distinct behaviors controlled, at least in part, by different genetic factors related to different dopaminergic mechanisms.

Animals↗

Pharmacological evidence for a role of D2 dopamine receptors in the defensive behavior of the mouse.

In this study the role of the DA system in the expression of defensive behavior of the mouse was investigated. C57BL/6 mice subjected to three daily defeat experiences (24 h apart) exhibited an increase of defensive behaviors (upright and sideways postures and escape) as well as a decrease of activity and a decrease of social investigation compared with undefeated mice (controls) when confronted with nonaggressive Swiss mice 24 h after the last aggressive confrontation. The selective D2 DA receptor antagonist (-)-sulpiride administered before confrontation with nonaggressive opponents (fourth day) dramatically decreased defensive behaviors and produced an increase of social investigation. The selective D1 DA receptor antagonist SCH 23390 did not affect either defence or social investigation. In further experiments the behavioral effects of the selective D1 agonist SKF 38393 and of the selective D2 agonist LY171555 on naive C57BL/6 mice interacting with nonaggressive opponents of the same strain were assessed. SKF 38393 in doses up to 30 mg/kg did not produce any significant behavioral changes while LY171555 produced a clear-cut dose-dependent increase of defensive behavior as well as a decrease of social investigation and activity and an increase of immobility. The behavioral profile produced by the D2 agonist did not differ from that produced by defeat experiences. These results indicate that D2 receptors play a major role in the expression of defensive behavior in the mouse. The hypothesis that alteration in D2 receptor functioning may produce hyperdefensiveness possibly due to altered perceptive processes is discussed.

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

Age-dependent changes of brain GABA levels, turnover rates and shock-induced aggressive behavior in inbred strains of mice.

Shock-induced aggressive behavior (SIAB) is absent or very weak in C57BL/6 (C57) mice at the age of 12 weeks while it reaches high levels at the age of 20 weeks. This age-dependent increase of aggressive responses is absent in DBA/2 (DBA) mice. Aggressive C57 mice (20 week old) are characterized by lower GABA levels in amygdala, striatum and substantia nigra than both non-aggressive C57 (12 week old) and DBA mice (12-20 week old). Concerning turnover rate, C57 mice at the age of 20 weeks show lower turnover rate values in cerebellum and raphe and higher values in septum in comparison with 12 week old mice of the same strain. These results are discussed in terms of the role of GABA function in brain areas which are involved in the control of emotionality and aggressive behavior.

Age Factors↗

Chronic exposure to a novel odor increases pups' vocalizations, maternal care, and alters dopaminergic functioning in developing mice.

This study was designed to assess the stress effect of manipulation of the olfactory environment in developing mice. In a first experiment it was found that mouse pups could be stressed (as measured by an increase in ultrasonic calls) by removing the litter from the dam for 15 min/day for the first 14 days of life and exposing them to a novel odor (clean bedding). This stress procedure also produced a long-term modification in maternal behavior. The stress response (ultrasounds) and the modification of maternal behavior were prevented by providing the litter with home cage bedding during maternal separation. In a second experiment it was demonstrated that early stress influenced apomorphine-induced wall climbing behavior in 15-day-old mice, suggesting stress-induced alterations in the dopaminergic system. Pups exposed to clean bedding during infancy exhibited more wall climbing behavior than pups never separated from the mother. Moreover, preventing the early stress response during mother-offspring separation, by providing pups with home cage bedding, eliminated the increase in apomorphine-induced wall climbing. Taken together these results suggest that olfactory cues are decisive in characterizing stressful situations inducing both immediate and long-lasting effects in mouse pups.

Animals↗