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S Cabib

Publications and source records attributed to S Cabib.

At least 37 records · Page 2Linked to original sources
PubMed1997

Brain dopamine receptor plasticity: testing a diathesis-stress hypothesis in an animal model.

A wealth of clinical data supports a major role of genetic liability as well as of altered brain dopamine (DA) functioning in different types of behavioural disturbances. Genetic influence on behaviour involves multiple genes, rather than one or two major genes, as well as non-genetic sources of variance. Thus, in recent years, increasing attention has been devoted to the involvement of stressful experiences (life events) in the development and expression of psychopathology. Moreover, a diathesis-stress hypothesis has been proposed, which suggests that the environmental factors (stress) are not specific for a given pathology, whereas genetic factors (diathesis) are. Results obtained in an animal model offer support to this hypothesis. Indeed, mice of the C57BL/6 and DBA/2 inbred strains are equally susceptible to stress but develop different behavioural disturbances related to different alterations of brain DA receptors. Moreover, quantitative trait loci (QTL) associations in the C57 (B) x DBA (D) recombinant inbred (RI) strains indicate a number of provisional QTLs influencing the behavioural effect of stress. Finally, the results of this analysis suggest the involvement of regulatory factors related to stress response and neural or synaptic plasticity in the control of brain DA receptor plasticity.

Animals↗
PubMed1997

Parallel strain-dependent susceptibility to environmentally-induced stereotypies and stress-induced behavioral sensitization in mice.

Food restriction (9 days) promoted stereotyped behavior in drug-free mice of the DBA/2 (DBA), but not in those of the C57BL/6 (C57), inbred strain. Indeed, behavior presented by food-restricted mice of the DBA strain within the home cage was characterised by a very high response rate within a single response: cage cover climbing. Moreover, enhanced climbing in food-restricted mice of the DBA strain was also observed in a test designed to detect stereotypic effects of drugs in mice. Stereotypic behavior in DBA mice did not depend on nutritional status because: 1. No stereotypies were observed in DBA mice food-deprived for 15 h; 2. no strain-dependent differences in weight loss were observed; and 3. enhanced cage cover climbing was still evident in DBA mice following 24 h of free feeding. Finally, food-restricted DBA mice showed long-lasting sensitization to the locomotor effects of systemic amphetamine, indicating stress-induced behavioral sensitization in this strain of mice. By contrast, no sign of behavioral sensitization was observed in food-restricted mice of the C57 strain. These results indicate that restricted feeding promotes stereotyped behavior, as well as behavioral sensitization to amphetamine, in mice. Moreover, the observed parallelism between strain-dependent susceptibility to environmentally-induced stereotypies and behavioral sensitization supports the hypothesis that these phenomena share common neuro-biological bases.

Animals↗
PubMed1997

Strain-dependent effects of D2 dopaminergic and muscarinic-cholinergic agonists and antagonists on memory consolidation processes in mice.

The interaction between muscarinic-cholinergic and dopaminergic systems in the modulation of memory storage of Y-maze discrimination (YMD) task was examined in C57BL/6 and DBA/2 strains of mice. In C57BL/6 mice, post-training systemic (i.p.) administration of the D2-agonist quinpirole facilitated retention and the D2-antagonist (-)-sulpiride impaired retention. Opposite effects were observed in DBA/2 strain. The facilitating or impairing effects of quinpirole and (-)-sulpiride were blocked by simultaneous post-training administration of muscarinic-cholinergic agonists and antagonists. The memory enhancing effects of the cholinergic agonist oxotremorine were not blocked by simultaneous administration of sulpiride in C57BL/6 mice or quinpirole in DBA/2 mice. Furthermore, the memory impairing effects of the cholinergic antagonist atropine were not blocked by simultaneous administration of quinpirole in C57BL/6 mice or sulpiride in DBA/2 mice. These findings indicate that the effects of D2-receptor agonists and antagonists on retention of YMD task are strain-dependent and mediated through muscarinic-cholinergic mechanisms.

Animals↗
PubMed1997

Psychopharmacology of dopamine: the contribution of comparative studies in inbred strains of mice.

Comparative studies of behavioral responses to centrally acting drugs in inbred strains of mice which show differences in brain neurotransmitter activity represent a major strategy in the investigation of the neurochemical bases underlying behavioural expression. Moreover, these studies represent a preliminary stage in behavioral genetic research since they allow quantitative scales to be established and suggest correlations to be tested in recombinant inbred strains. The present review evaluates results obtained in mice of the C57BL/6 (C57) and DBA/2 (DBA) inbred strains which have been used for studies of the behavioral pharmacology of dopamine (DA) and investigated for the functional and anatomical characteristics of their brain DA systems. Differences between C57 and DBA strain involve susceptibility and sensitivity as well as qualitative differences in the type or direction of the behavioral effects of DA agonists. Moreover, data on strain-dependent differences for DA metabolism, release and receptor densities and distribution provide important indications about the relationship between behavioral and central effects of DA agonists and, more generally, about the involvement of brain DA in behavior. Comparative studies in C57 and DBA mice have also revealed differences in susceptibility to context-dependent, context-independent and stress-induced behavioral sensitization to psychostimulants. Consequently, they support the view that the term "behavioral sensitization" may define different phenomena in which different, independent genotype-related factors play a major role. Finally, studies on the behavioral and central effects of stressful experiences in C57 and DBA mice together with psychopharmacogenetic analyses, indicate that different symptomatological profiles may derive from genotype-dependent adaptation of brain DA receptors to environmental pressure.

Animals↗
PubMed1997

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

Post-training administration of anandamide (1.5, 3, 6 mg/kg) dose-dependently impairs the 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, as 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. Pretreatment with either selective D1 or D2 dopamine (DA) receptor agonists, SKF 38393 and quinpirole, at doses that were ineffective when given alone (5 and 0.25 mg/kg, respectively), antagonized the effects of anandamide on memory consolidation, suggesting that D1 and D2 receptors are similarly involved in the effects of anandamide on memory consolidation. These results are discussed in terms of a possible inverse relationship between the modulation of memory processes by endogenous cannabinoid and DA systems.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Opposite strain-dependent effects of post-training corticosterone in a passive avoidance task in mice: role of dopamine.

Post-training administration of corticosterone (0.1-1 mg/kg) dose-dependently improves retention of an inhibitory avoidance response in C57BL/6 mice, whilst impairing it in the DBA/2 strain. The effects on retention performance induced by the hormone in C57BL/6 and DBA/2 mice appear to be due to an effect on memory consolidation. In fact, they were observed when the drug was given at short, but not long, periods of time after training, i.e., when the memory trace is susceptible to modulation. In the absence of pharmacological manipulations, the two strains showed a significant increase of plasma corticosterone levels 15 min after passive avoidance training that disappeared within 30 min, and similar step-through latencies on the test day. However, although no strain differences were observed for sensitivity to shock thresholds, the increase in plasma corticosterone levels elicited by passive avoidance training was more pronounced in mice of the DBA/2 strain (+160%) than in C57BL/6 mice (+52%). Moreover, DBA/2 mice were characterised by a higher number of either Type I or Type II corticosteroid receptors in the hippocampus in comparison with C57BL/6 mice. Finally, the strain-dependent effects of an intermediate dose of corticosterone were enhanced by pretreatment with either the selective D1 or D2 dopamine (DA) receptor agonists SKF 38393 and LY 171555 and reversed by pretreatment with either selective D1 or D2 DA receptor antagonists SCH 23390 and (-)-sulpiride administered at per se non-effective doses. The present results indicate that studies in inbred strains of mice can dissect opposite effects of corticosterone on memory consolidation possibly due to its action at different steps or components of the multiphasic pathway of memory consolidation. Moreover, they suggest that some of these steps involve an interaction between the hormone and brain DA system.

Animals↗
PubMed1996

Dopamine-N-methyl-D-aspartate interactions in the modulation of locomotor activity and memory consolidation in mice.

This study explores the functional interaction between glutamatergic and dopaminergic systems in the modulation of two behavioral responses: locomotor activity and memory consolidation assessed with one-trial inhibitory avoidance. In agreement with previous reports, the NMDA receptor antagonist, (+)-MK-801 ((+)-5-methyl-10,11-dihydro(a,d) cyclohepten-5,10-imine hydrogen maleate), dose dependently enhanced locomotor activity in mice. The selective dopamine D1 receptor antagonist SCH 23390 at doses up to 0.05 mg/kg was unable to affect MK-801-induced locomotor activity, while (-)-sulpiride, but only at high doses (30 mg/kg), and haloperidol (0.05 mg/kg) blocked the MK-801 effect. Hypermotility induced by MK-801 was enhanced by repeated administration of haloperidol (once daily administration for 14 days of 4 mg/kg) or (-)-sulpiride (125 mg/kg), but not SCH 23390 (0.5 mg/kg). Dopamine D1 (SKF 38393)- and D2 (quinpirole)-selective agonists enhanced retention of one-trial inhibitory avoidance performance whilst NMDA receptor antagonists 3-(2-D-carboxypiperazin-4-yl)propyl-1-phosphoric acid (CPP) and MK-801 impaired it. Moreover we observed that the NMDA receptor antagonist-induced impairment of memory consolidation was attenuated by subeffective doses of SKF 38393 (5 mg/kg) and quinpirole (0.25 mg/kg). Impairment of the response induced by post-trial injections of CPP and MK-801, in the one-trial inhibitory avoidance test, was highly enhanced by 14 days of daily administration of haloperidol (4 mg/kg), sulpiride (25 mg/kg) but also SCH 23390 (0.5 mg/kg). These results suggest that different neural mechanisms underlie the functional interaction between the two neural systems in the modulation of these behavioral responses. Further, the results of the chronic study revealed a possible heterologous regulation of NMDA receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Strain-dependent effects of cocaine on memory storage improvement induced by post-training physostigmine.

Post-training administration of the inhibitor of cholinesterase enzymes, physostigmine, dose-dependently (0.025-0.4 mg/kg) improved retention of an inhibitory avoidance response in C57BL/6 (C57) as well as in DBA/2 (DBA) mice, the latter being more responsive than C57 mice. The effects on retention performance induced by physostigmine in C57 and DBA mice appeared 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, which is when the memory trace is susceptible to modulation. Moreover, these effects are not to be ascribed to 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. Post-training administration of cocaine (1-5 mg/kg) dose-dependently improved retention of an inhibitory avoidance response in C57 mice, while impairing it in the DBA strain, thus confirming previous results (Puglisi-Allegra et al. 1994b). Pretreatment with cocaine at ineffective doses as well as at an effective one potentiated the effects of an ineffective as well as of an effective dose of physostigmine in C57 mice, while it antagonized the effects of the inhibitor of cholinesterase enzymes on memory consolidation in DBA mice. The present results indicate that the indirect DA receptor agonist cocaine affects physostigmine action on memory consolidation in an opposite manner in the two inbred strains, pointing to genotype-dependent interaction between cholinergic and dopaminergic activity in memory consolidation.

Animals↗
PubMed1996

Dose-dependent aversive and rewarding effects of amphetamine as revealed by a new place conditioning apparatus.

Amphetamine-induced place conditioning was evaluated in mice using a newly designed apparatus. It was demonstrated that this apparatus provides a neutral set of cues devoid of rewarding or aversive properties and can reveal place preference or aversion after pairings with drugs (amphetamine and morphine for preference and naloxone for aversion) known to produce such effects. Moreover, repeated pairings of environmental cues with either 2 or 3 mg/kg d-amphetamine resulted in significant conditioned place preference on a drug free test, whilst repeated pairings with a lower dose of the drug (1 mg/kg) resulted in significant conditioned place aversion. Finally, a small number of mice showed opposite responses in comparison with group means at low as well as at high doses of amphetamine. These results suggest that amphetamine may promote conditioned place preference or avoidance depending on dosage and individual susceptibility.

Amphetamine↗
PubMed1996

Stress, depression and the mesolimbic dopamine system.

The present review was aimed at re-evaluating results obtained from animal models of depression based on experimental stressors in the light of the most recent data on the effects of stress on mesolimbic dopamine (DA) functioning. The data reviewed reveal that the effects of stressful experiences on behaviour and on mesoaccumbens DA functioning can be very different or even opposite depending on the behavioural controllability of the situation, the genetic background of the organism and its life history. Exposure to a single unavoidable/uncontrollable aversive experience leads to inhibition of DA release in the accumbens as well as to impaired responding to rewarding and aversive stimuli. Moreover, the data reviewed indicate a strong relationship between these neurochemical and behavioural effects and suggest that they could model stress-induced expression and exacerbation of some depressive symptoms such as anhedonia and feeling of helplessness caused by life events as well as syndromal depression provoked by traumatic experiences in humans. Repeated and chronic stressful experiences can reduce the ability of stressors to disrupt behaviour, induce behavioural sensitisation to psychostimulants and promote adaptive changes of mesolimbic DA functioning. Opposite neural and behavioural changes, however, can be promoted in specific environmental conditions (repeated variable stressful experiences) or in genetically predisposed individuals. Thus, depressive symptoms may not represent the necessary outcome of stress experiences but be promoted by specific environmental conditions and by a genetically determined susceptibility.

Animals↗
PubMed1996

Psychopharmacology of memory modulation: evidence for multiple interaction among neurotransmitters and hormones.

Experimental results are reviewed which indicate that memory storage can be altered by a number of post-training treatments that affect different hormones and neurotransmitters. Moreover, evidence was reported which suggests that the action of treatments effective on memory processes involves interactions among different systems, consistently with the complexity of brain systems. In the last decade, inbred strains have been exploited to investigate the role of neurotransmitter and hormone systems in learning and memory, leading to behavioural and neurochemical correlations based on strain differences that provide unique information on the biological systems underlying behaviour. Research carried out on the inbred strains of mice C57BL/6 (C57) and DBA/2 (DBA), demonstrates that the genetic makeup plays an important role in modulating response to drug administration. Thus, recent results have shown that in C57 mice, similarly to what occurs in outbred strains of mice or in rats, GABAergic agonists impair memory and antagonists improve it, whilst the opposite is evident in the DBA strain. By contrast, post-training administration of selective D1 or D2 agonists impairs and post-training administration of selective antagonists improves retention in DBA mice, whilst these agents have opposite effects in the C57 strain. Dose- and strain-dependent effects are evident also following post-training corticosterone as well as opioid agonists and antagonists administration. On the other side, these two strains react similarly to oxotremorine (improvement) and to atropine (impairment) administration, DBA mice being more responsive to the effects of both drugs than C57 mice. Data on the interactions between agents acting upon different neurotransmitter and/or hormonal systems in these strains indicate strain-dependent synergistic or antagonistic interactions among some of these systems, pointing to inbred strains of mice as an important methodological tool in the study of neural and hormonal factors involved in emotion and in its effects on cognition. In particular, these studies have been carried out on inbred strains of mice from which recombinant inbred (RI) strains are available that have recently been proposed as a choice experimental method in psychopharmacogenetics.

Animals↗
PubMed1996

Different effects of repeated stressful experiences on mesocortical and mesolimbic dopamine metabolism.

The effects of repeated stressful experiences (10 min restraint, daily) on the levels of dopamine and metabolites in the nucleus accumbens septi and frontal cortex were evaluated. In naive mice, restraint stress increased 3-4-dihydroxyphenylacetic acid, homovanillic acid, and 3-methoxytyramine levels in the nucleus accumbens and 3-4-dihydroxyphenylacetic acid levels in the frontal cortex. The effects of stress on 3-methoxytyramine and homovanillic acid levels in the nucleus accumbens septi disappeared within five days of daily restraint experiences and the increase in 3-4-dihydroxyphenylacetic acid levels was no longer evident by the 10th day. By contrast, the response of mesocortical dopamine system to restraint (increased 3-4-dihydroxyphenylacetic acid levels) was unaffected by either five or 10 days of exposure to the stressor. Moreover, 10 min of restraint were still able to increase 3-4-dihydroxyphenylacetic acid levels in the frontal cortex of mice repeatedly exposed (nine days) to 120 min restraint. These results indicate that the mesolimbic and the mesocortical dopamine systems adapt differently to repeated exposure to a stressor.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Strain-dependent effects of dopamine agonists on acetylcholine release in the hippocampus: an in vivo study in mice.

The effects of selective D1 or D2 dopamine receptor agonists and the indirect dopamine agonist cocaine on hippocampal acetylcholine release in mice of the C57BL/6 and DBA/2 inbred strains were investigated using intracerebral microdialysis. The D1 SKF 38393 (10, 20, 30 mg/kg, i.p.), the D2 agonist LY 171555 (0.5, 1, 2 mg/kg, i.p.) and cocaine (5, 10, 15 mg/kg, i.p.) all increased, dose-dependently, acetylcholine release in the hippocampus of C57BL/6 mice. Both the D1 agonist and cocaine did not produce any significant effect in DBA/2 mice. In the latter strain, however, LY 171555 produced a decrease in acetylcholine release that was evident after 60 min from injection of the doses of 0.5 and 1 mg/kg, but not at the dose of 2 mg/kg. The effects observed in C57BL/6 mice as well as those produced by low doses of LY 171555 in the DBA/2 strain were consistent with previous results obtained in rats. The present results indicate major strain-dependent differences in the effects of dopamine agonists on hippocampal acetylcholine release in mice. Moreover, they suggest a complex genotype-related neural organization of dopamine-acetylcholine interactions in the mesolimbic system. Finally, the strain differences in the effects of the dopamine agonists on hippocampal acetylcholine release parallel previously reported strain differences in the effects of these substances on memory consolidation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

A comparison of the behavioral effects of minaprine, amphetamine and stress.

Different types of clinically effective antidepressants prevent the behavioral effects of experimental stress, and some of these treatments affect mesolimbic dopamine (DA) functioning. Animal studies have demonstrated that repeated psychostimulant administration and repeated or chronic stressful experiences also affect mesolimbic DA functioning. These results could suggest homologies among stress, psychostimulants and antidepressants. The present experiments show that either repeated stress (120 min restraint daily for 10 consecutive days) or subchronic treatment with the antidepressant minaprine (5 mg/kg daily for 10 consecutive days) significantly reduced the inhibitory effect of 120 min of restraint on climbing, a behavioral response dependent on mesolimbic DA functioning. However, the antidepressant did not induce the altered sensitivity of presynaptic DA receptors promoted by repeated stress. Chronic stressful experience (13 days of food restriction) and repeated amphetamine (2.5 mg/kg daily for 10 consecutive days) were as effective as subchronic minaprine in reducing immobility in the Porsolt's swimming test. However, whilst both stress and amphetamine enhanced struggling, minaprine promoted swimming. Finally, chronically stressed mice and mice pretreated with amphetamine showed enhanced sensitivity to amphetamine-induced locomotion, whilst this effect was absent in animals pretreated with the antidepressant. These results indicate that although chronic and repeated stress as well as amphetamine have some antidepressant-like behavioral effects, their mode of action could be different from that of clinically active substances.

Amphetamine↗
PubMed1995

Effects of the NMDA-antagonist, MK-801, on stress-induced alterations of dopamine dependent behavior.

The effects of pretreatment with the non-competitive NMDA antagonist (+)MK-801 on the behavioral alterations induced by repeated restraint stress were investigated. Repeatedly stressed (restraint stress 2 h a day x 10 days) mice showed enhanced sensitivity to the inhibitory effects of a low dose of direct dopamine agonist, apomorphine (0.25 mg/kg), on climbing behavior. On the other hand, no changes were observed for the stimulatory effect of the high dose of apomorphine (3 mg/kg) on this behavioral response. Mice pretreated with MK-801 (0.15 mg/kg) before the stressful experience did not show altered response to the low dose of apomorphine (0.25 mg/kg). Finally, ten daily injections with 0.15 mg/kg MK-801 did not affect the behavioral response to the low dose of apomorphine, but enhanced the stimulatory effect of the high dose of the dopaminergic agonist on climbing behavior. Therefore, it is possible that the protective action of MK-801 against stress-induced behavioral alteration is due to changes in sensitivity of postsynaptic receptors.

Animals↗
PubMed1995

Paw preference and brain dopamine asymmetries.

The hemispheric content of dopamine and its metabolites in the frontal cortex, caudatus putamen and nucleus accumbens septi was evaluated in relation to behavioral lateralization assessed by paw preference. Three groups of C3H/He mice were selected on the basis of their performance in the paw preference test (left-handed, ambidextrous and right-handed) and levels of dopamine and its metabolites were measured in the two hemispheres of each group. Mice showed significant differences in hemispheric content of dopamine and 3-4 dihydroxyphenylacetic acid in the nucleus accumbens septi depending on the behavioral lateralization as expressed by paw preference. The hemispheric dominance (right hemisphere/right hemisphere + left hemisphere content of dopamine and metabolites x 100) was also calculated for each mouse. Significant differences in hemispheric dominance for dopamine, 3-4 dihydroxyphenylacetic acid and 3-methoxytyramine in the nucleus accumbens were found between right-handed and left-handed mice. This dominance was ipsilateral to the preferred paw: % right hemisphere/total content of dopamine and its metabolites were lowest in left-handed, highest in right-handed and intermediate in ambidextrous mice. Finally, individual % right hemisphere/total content for dopamine, 3-4 dihydroxyphenylacetic acid and 3-methoxytyramine in the nucleus accumbens positively correlated with individual paw preference scores. The analysis of the other brain areas did not reveal any significant effect. These results suggest a strong relationship between mesoaccumbens dopamine asymmetries and both the direction and the intensity of behavioral lateralization as expressed by paw preference in mice.

3,4-Dihydroxyphenylacetic Acid↗