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S Cabib

Publications and source records attributed to S Cabib.

At least 55 records · Page 3Linked to original sources

Effects of subchronic minaprine on dopamine release in the ventral striatum and on immobility in the forced swimming test.

Subchronic (5 mg/kg daily for 9 consecutive days) but not acute minaprine treatment enhanced in vivo dopamine release in the limbic part of the striatum of rats as revealed by intracerebral microdialysis. Moreover, the same subchronic treatment with minaprine reduced immobility in the forced swimming test. The anti-immobility effect of minaprine was not evident after a single injection of the antidepressant. Finally, the subchronic treatment with minaprine was devoid of effects in an activity test. These results suggest that enhanced dopaminergic transmission may contribute to the pharmacological and clinical profile of this drug.

Animals↗

Influence of early life events on immune reactivity in adult mice.

The effects of postnatal manipulations on different immune parameters were investigated in adult female mice. Postnatal stress consisted of a 15-min daily exposure to clean bedding (temperature maintained at 35 degrees C) for the first 2 weeks of life in the absence of the mother but in the presence of littermates. Controls were unhandled until weaning. At 60 days of age, female mice stressed during postnatal development showed enhanced immune reactivity as assessed by NK-cell activity and T-cell mitogenesis in comparison with unhandled mice. By contrast, B-lymphocyte proliferation induced by lipopolysaccharide (LPS) was not affected by alterations of postnatal environment. Furthermore, the association between immune reactivity and behavioral lateralization observed in adult mice was not altered by postnatal stress.

Aging↗

Strain-dependent effects of post-training cocaine or nomifensine on memory storage involve both D1 and D2 dopamine receptors.

Post-training administration of cocaine (1-10 mg/kg) or nomifensine (1-10 mg/kg) dose-dependently improves retention of an inhibitory avoidance response in C57BL16 mice, while impairign it in the DBA/2 strain. The effects of retention performance induced by the psychostimulant and the dopamine (DA) reuptake blocker in C57BL/6 and DBA/2 mice appear to be due to an effect on memory consolidation. In fact, they were observed when drugs were given at short, but not long, periods of time after training, i.e. when the memory trace is susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or non-specific 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 affected by the post-training drug administration. The strain-dependent effects of an intermediate dose (5 mg/kg) of both cocaine and nomifensine were reversed by pretreatment with either selective D1 or D2 DA receptor antagonist SCH 23390 and (-)-sulpiride administered at per se non-effective doses (0.025 and 6 mg/kg, respectively), thus suggesting that D1 and D2 receptor types are similarly involved in modulating memory processes. These results show that the effects of cocaine on memory consolidation are related to to its dopaminergic action, since they are similar to those produced by nomifensine and, what is more important, are antagonized by pretreatment with DA receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Post-training minaprine enhances memory storage in mice: involvement of D1 and D2 dopamine receptors.

Post-training administration of minaprine (2.5, 5 and 10 mg/kg) dose-dependently improved retention of an inhibitory avoidance response in mice. Animals receiving nine daily injections of 5 mg/kg and administered a challenge dose post-training showed an improvement in memory consolidation similar to that produced by acute injection of 10 mg/kg. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. They were observed when drugs were given at short, but not long, periods of time after training, i.e. when the memory trace was susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or non-specific action of the drugs on retention performance, as the latencies during the retention test of those mice that had not received a footshock during training were not affected by post-training drug administration. The effects of an acutely injected dose (10 mg/kg) of minaprine as well as those of a challenge dose (5 mg/kg) of the drug administered to repeatedly treated animals were reversed by pretreatment with either selective D1 or D2 dopamine receptor antagonists SCH 23390 and (-)-sulpiride administered at per se non-effective doses (0.025 and 6 mg/kg, respectively), thus suggesting that D1 and D2 receptor types are similarly involved in the effects of minaprine on memory consolidation. These results show that minaprine improves memory consolidation and that repeated drug administration leads to potentiation of this effect. Moreover, the effects of minaprine on memory consolidation are related to its dopaminergic action.

Animals↗

The effects of morphine on memory consolidation in mice involve both D1 and D2 dopamine receptors.

Post-training administration of morphine (0.25, 0.5, or 1 mg/kg) dose-dependently impairs retention of an inhibitory avoidance response in mice. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. In fact, they were observed when drugs were given at short, but not long, periods of time after training, i.e., when the memory trace was susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or nonspecific action of the drugs on retention performance, because the latencies during the retention test of those mice that had not received a footshock during the training were not affected by post-training drug administration. Pretreatment with either selective D1 or D2 dopamine (DA) receptor antagonists SCH 23390 and (-)-sulpiride administered at per se noneffective doses (0.025 and 6 mg/kg, respectively) potentiated the effects of morphine, while either selective D1 or D2 receptor agonists SKF 38393 and LY 171555 at per se noneffective doses (5 and 0.25 mg/kg, respectively) antagonized the effects of the opiate on memory consolidation. No significant differences were evident between the effects of D1 and D2 receptor active compounds, thus suggesting that D1 and D2 receptor types are similarly involved in the effects of morphine on memory consolidation, in agreement with previously reported results. These results are discussed in terms of a possible inverse relationship of endogenous opioid and DA systems in the brain that are involved in memory processes.

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

Opposite responses of mesolimbic dopamine system to controllable and uncontrollable aversive experiences.

It has been previously shown that rodents exposed to stressful experiences show a biphasic response of the mesolimbic dopamine (DA) system, that is, initial increase of DA release followed by a decrease below control levels (Puglisi-Allegra et al., 1991). Evidence is now presented showing that mice exposed to a series of foot shocks show an increase of DA release in the nucleus accumbens septi (NAS) if they are allowed to control the shock experience (shocked condition) and a decrease of DA release in this brain area if they are not allowed to exert any control (yoked condition). These results indicate that escapable/controllable and inescapable/uncontrollable aversive experiences elicit opposite responses from the mesolimbic DA system. Mice exposed to the apparatus without receiving shock (sham condition) show a time-dependent biphasic evolution mesolimbic DA release in line with previous reports indicating that confinement in an unknown environment represents a stressful experience for mice. Moreover, exposure to the sham condition for a time comparable to the duration of shock and yoked exposure induces a mesolimbic DA response only quantitatively different from the response of the yoked group but qualitatively different from the response of the shocked mice. These results suggest that in environmental conditions that allow behavioral control, enhanced mesolimbic DA release is maintained regardless of the intensity of the aversive stimuli. On the other hand, evaluation of changes in acid DA metabolites levels in the frontal cortex (FC) of mice exposed to the shocked, yoked, and sham conditions suggests that stressful experiences characterized by a different intensity of the aversive stimuli could elicit graded responses in the FC DA system.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Effects of postnatal stress on dopamine mesolimbic system responses to aversive experiences in adult life.

The effects of postnatal stress on mesolimbic dopamine (DA) functioning in 90-day-old mice were investigated. Postnatal stress consisted of 15 min daily exposure to clean bedding (CB) in the absence of the mother for the first two weeks of life. Controls were daily exposed to home cage bedding (HCB) in the absence of the mother. A single brief (5-10 min) exposure to restraint produced a clear-cut increase in DA metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT)) in the nucleus accumbens septi (NAS) of adult HCB but not CB mice. Moreover, when tested in an elevated plus maze, CB mice showed more exploration and reduced fearfulness in comparison with HCB mice. Taken together, these results indicate reduced emotional reactivity in adult mice repeatedly stressed during postnatal development. Moreover, HCB mice but not CB mice showed altered behavioral responsiveness to apomorphine following repeated restraint stress (10 daily 120 min) in adult life, although no difference in the behavioral response to either a low or a high dose of apomorphine was observed in adult unstressed mice of the CB and HCB groups. These results indicate that the effects of early experiences on brain DA functioning may not be evident in basal conditions and be revealed only under environmental pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Repeated stressful experiences differently affect the time-dependent responses of the mesolimbic dopamine system to the stressor.

The increase in mesolimbic dopamine (DA) release observed during the first 40 min of 120 min restraint in naive rats is not evident in repeatedly stressed animals (daily 60 min restraint, for 5 days). However, repeatedly stressed rats show a significant decrease in DA release from 80 min of restraint onwards which is not observable in naive rats. These results indicate that repeated stressful experiences do not produce habituation but alter the response of mesolimbic DA system to the stressor. Moreover, they point to a possible neuronal mechanism underlying stress-induced depression.

3,4-Dihydroxyphenylacetic Acid↗

Strain-dependent effects of post-training GABA receptor agonists and antagonists on memory storage in mice.

Post-training administration of the GABA-A and GABA-B receptor agonists muscimol and baclofen dose-dependently impaired retention of an inhibitory avoidance response in C57 mice, while improving memory consolidation in the DBA strain. By contrast, picrotoxin (blocker of GABA-activated ionophores), bicuculline (GABA-A antagonist) and CGP 35348 (GABA-B antagonist) dose-dependently improved retention in C57 mice and impaired it in DBA mice. These effects cannot be ascribed to non-specific actions of the drugs on retention performance, as the latencies during the retention test of those mice that had not received footshock during the training were not lengthened by the post-training drug administration. The effects on retention performance induced by GABA agonists and antagonists are probably due to an effect on memory consolidation, since they are observed when the drugs are given at short, but not at long, intervals after training. These results are discussed in terms of possible interaction of GABA systems with endogenous opioid and dopamine systems, whose activation has been shown to produce strain-dependent effects on memory processes. The possible utilization of these results for a genetic behavioral approach with recombinant inbred (RI) mice is also considered.

Animals↗

Effects of acute and repeated exposure to stress on the hypothalamo-pituitary-adrenocortical activity in mice during postnatal development.

Hypothalamo-pituitary-adrenocortical (HPA) response to a mild stressful procedure was investigated in mice at Days 8, 10, 12, and 14 of postnatal development. Pups that were removed from the dam and exposed to a novel odor (clean bedding) for 15 min showed higher plasma corticosterone levels than pups whose mother was removed from the cage for 15 min or unhandled pups at all ages, although statistically significant differences were only evident at Days 12 and 14. Lower HPA axis responding in younger mice was not due to immaturity since 8-day-old mice showed a significant and larger increase of plasma corticosterone levels when separated from the mother and isolated from littermates in the absence of bedding. Mice daily exposed to clean bedding (15 min) for the first 13 days of life did not show reduced plasma corticosterone response when reexposed to the stressor at 14 days of age. Conversely, increased plasma corticosterone levels in dams in response to removal of pups was not detectable after repeated exposure to this manipulation (14 days) regardless of the procedure their pups were submitted to, thus ruling out a role of maternal corticosterone passing through the milk on which the pups were fed. These results demonstrate that 15 min exposure to clean bedding is a noninvasive procedure able to elicit HPA axis response in developing mice over a wide age range without producing habituation.

Animals↗

Nonhuman behavioral models in the genetics of disturbed behavior.

The development of the association method in which genetic markers match quantitative traits had led to quantitative trait loci (QTL) interval mapping. The association method has been extensively used in animal behavior genetics. Animal research allows more suitable linkage studies and detailed assessment of cellular and subcellular components of the central nervous system that may play a crucial role in the development susceptibility to behavioral disorders. Moreover, experimental designs in the laboratory setting allow genotype x environment interactions to be controlled, thus possibly providing more information on the role of nongenetic factors in gene expression. Experimental results are discussed which indicate that animal studies will provide a sort of test for hypotheses arising in clinical settings, allowing gene-product and product-behavior pathways to be examined at molecular levels when the gene accounts for a very small amount of genetic variance. In such a perspective, new molecular biology approaches and behavior genetics in nonhuman species could provide useful tools in the assessment of the genetic as well as nongenetic factors that lead to psychopathology.

Affective Disorders, Psychotic↗

Chronic stress induces strain-dependent sensitization to the behavioral effects of amphetamine in the mouse.

Following 10 days of daily restraint stress, sensitization developed to the stimulatory effect of amphetamine on locomotion in DBA/2 but not in C57BL/6 mice tested 24 h after the last stressful experience regardless of their being naive or habituated to the test cages. Saline-injected C57BL/6 mice, however, showed an increase of locomotion 24 h after chronic stress treatment. Chronically stressed mice of the two strains did not exhibit any alteration of dopamine and metabolites (3-4-dihydroxphenylacetic acid, homovanillic acid, and 3-methoxytyramine) levels in the frontal cortex, caudatus putamen, or nucleus accumbens septi, thus ruling out that stress-induced alteration of basal dopamine metabolism affected the behavioral response to amphetamine challenging in DBA/2 mice. Ten daily amphetamine injections (5 mg/kg) did not significantly modify the behavioral response to amphetamine in either strain of mice tested 24 h after the end of the chronic treatment and did not increase locomotion in saline-injected C57BL/6 mice. Finally, chronically stressed hybrids B6D2F1 did not show sensitization to the locomotor effects of amphetamine, suggesting a dominant mode of inheritance in the response to chronic stress of the C57BL/6 strain.

3,4-Dihydroxyphenylacetic Acid↗

Strain-dependent effects of post-training dopamine receptor agonists and antagonists on memory storage in mice.

Post-training administration of the selective D1 or D2 agonists SKF 38393 and LY 171555 dose dependently impairs retention of an inhibitory avoidance response in DBA/2 mice. In agreement, the selective D1 or D2 antagonists SCH 23390 and (-)-sulpiride improve retention. These effects are opposite to those observed in the C57BL/6 strain, as previously reported. Moreover, B6D2F1 hybrids present a response to SKF 38393, LY 171555, SCH 23390, and (-)-sulpiride that parallels that of the C57BL/6 strain, thus suggesting that the neural mechanisms underlying the effects of DA agonists or antagonists on memory processes may be inherited through a dominant mode of inheritance.

Animals↗

Acute stress induces time-dependent responses in dopamine mesolimbic system.

Exposure to either restraint or footshock (3-60 min) induced similar biphasic alterations of 3-methoxytyramine (3-MT) concentrations (initial increase followed by decrease below control levels) in the nucleus accumbens septi (NAS) of mice, as revealed by tissue analysis. The only difference between the two stressors was the earlier onset of the decrease phase in the restrained mice. In both stressful conditions acid metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased throughout stress, while no significant changes in dopamine (DA) concentrations occurred. These data suggest biphasic alteration of DA release during prolonged stress exposure. The analysis of release in restrained conscious rats by in vivo microdialysis (10-240 min) showed a similar biphasic DA evolution (initial increase followed by decrease below baseline levels) in the NAS. The only difference from the previous experiment was the delayed onset of the decrease phase. Similar changes in DOPAC and HVA were also evident. Moreover, freed rats showed an immediate increase of DA release over baseline levels, also indicating that depletion of the neurotransmitter cannot account for the reduction of released DA. Taken together, these results support the hypothesis that biphasic alteration of DA transmission in the mesolimbic system is a general response to stress and suggest that the initial increase of DA release represents an arousal response while the subsequent decrease in DA release may be related to coping failure.

3,4-Dihydroxyphenylacetic Acid↗

Genotype-dependent effects of chronic stress on apomorphine-induced alterations of striatal and mesolimbic dopamine metabolism.

After 10 daily consecutive restraint experiences, DBA/2 (DBA) mice showed an increase of climbing behavior after injection of 0.25 mg/kg of the dopamine (DA) agonist apomorphine (APO), while no changes were observed following vehicle or 1 mg/kg of APO. By contrast, chronically stressed C57BL/6 (C57) mice showed a clear-cut decrease of climbing behavior at the dose of 0.25 mg/kg of APO and a similar, although less pronounced, effect of stress on the behavior of mice injected either with vehicle or with 1 mg/kg APO. The DA agonist at these same doses decreased 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) concentrations in the caudatus putamen (CP) and nucleus accumbens septi (NAS) of both strains. Higher DOPAC, HVA and 3-MT concentrations were evident in stressed DBA mice receiving 0.25 mg/kg but not 1 mg/kg of APO, in both CP and NAS. Concerning C57 mice, lower concentrations of the 3 metabolites were present at both doses of APO in the NAS of stressed mice in comparison with non-stressed animals, while no significant stress-related effects were evident in the CP. Non-significant differences between control and stressed mice of both strains were evident as regards DA concentrations in CP and NAS. These results suggest that repeated stressful experiences lead to a hyposensitivity of DA presynaptic receptors in DBA mice while they produce a sensitization of mesolimbic DA presynaptic receptors possibly accompanied by down-regulation of postsynaptic DA receptors in the C57 strain.

Animals↗

LY 171555-induced hyperdefensiveness in the mouse does not implicate benzodiazepine receptors.

In naive mice the selective D2 agonist LY171555 dose-dependently (0.5-5 mg/kg) induces defensive responses toward non-aggressive conspecifics. In order to investigate possible anxiogenic properties of the D2 agonist, its behavioural effects were compared with those produced by the benzodiazepine receptor inverse agonist methyl-beta-carboline-3-carboxylate(beta-CCM) in the elevated plus maze and in social interactions with non-aggressive opponents. When tested in the elevated plus maze, mice injected with LY 171555 (0.005-1 mg/kg) showed no decrease either of the number of entries or of the time spent in the open arms. At 5 mg/kg an actual increase of these two measures was observed. By contrast, beta-CCM (1-3 mg/kg) dose-dependently decreased both the number of entries and the time spent in the open arms without altering locomotion. The effects of beta-CCM were antagonized by the benzodiazepine receptor antagonist RO 15-1788 (3 mg/kg) showing a selective involvement of benzodiazepine receptors in their modulation. On the other hand, beta-CCM, (1-3 mg/kg) did not produce significant effects on defensive behaviour of mice interacting with non-aggressive opponents and the defensive responses of mice treated with 1 mg/kg LY 171555 were not prevented by 5 mg/kg chlordiazepoxide. These results show that DA D2-mediated hyperdefensiveness and anxiety modulated by benzodiazepine receptors are unrelated phenomena and suggest that this behavioural response may represent a model of those forms of fear-related reaction that do not respond to benzodiazepine treatment.

Aggression↗

D1 and D2 receptor antagonists differently affect cocaine-induced locomotor hyperactivity in the mouse.

Pretreatment with small, per se ineffective doses of the selective D1 antagonist SCH 23390 inhibited hyperactivity induced by cocaine. On the other hand, the classic neuroleptic haloperidol and the selective D2 antagonist metoclopramide prevented the stimulatory effects of cocaine on locomotion only at hypokinetic doses, while the atypical neuroleptic (-)-sulpiride, a selective D2 antagonist, did not produce significant effects when administered at the hypokinetic dose of 12 mg/kg. Finally, at low doses (-)-sulpiride dose-dependently potentiated the locomotor-stimulating effects of cocaine, an effect that is not shared either with haloperidol or with metoclopramide. These results are discussed in terms of different roles of DA receptor subtypes in the modulation of the stimulant effects of cocaine on locomotion.

Animals↗