Progress in brain research
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There has been significant recent growth in programmes evaluating preventive treatment for individuals exhibiting prodromal symptoms, at high risk of developing first-episode psychosis. Because of the tremendous human and economic burden of schizophrenia and other psychotic disorders, primary prevention modalities of even modest impact would likely have important public health consequence. Several published clinical trials suggest that antipsychotic medications have beneficial effects in either preventing or postponing the emergence of first-episode psychosis in individuals at high risk of psychosis. ⋯ In one such study, low-dose risperidone pre-treatment prevented behavioural abnormalities following neonatal hippocampal lesions, while higher risperidone pre-treatment was ineffective. These findings support the predictive validity of the neonatal hippocampal lesion model in identifying psychosis prevention interventions, provide theoretical support for the use of low-dose risperidone in prevention of first-episode psychosis and suggest the possibility that higher risperidone doses could be less effective than low dosages in this application. These observations also suggest a potential role for selective 5-HT(2A) receptor antagonists as drug development targets for psychosis prevention.
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Serotonin and dopamine are two monoamines which are known to interact with each other. Their role for suicidal behaviour, aggression and mood are reviewed in this chapter. We found a substantial amount of evidence for the relevance of a serotonin and dopamine model of aggression, and for aggression as a major risk factor for suicide. Evidence was found that serotonin and dopamine also may be involved in depressed mood, and possibly the individual's ability to cope with imminent suicidality.
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The neuropeptides arginine vasopressin (AVP) and oxytocin (OXT) are acknowledged as important modulators of diverse social behaviours. Here we discuss recent studies using intracerebral microdialysis to investigate the dynamics of AVP and OXT release patterns within distinct brain regions during the display of social behaviours in rats. Manipulation of local receptor-mediated actions of AVP and OXT via retrodialysis of either agonists or antagonists revealed the behavioural significance of changes in local neuropeptide release. ⋯ Interestingly, OXT released within the PVN during sexual activity in male rats was found to be associated with a robust decrease in anxiety-related behaviour up to 4h after mating. These data illustrate distinct modes of behavioural actions of AVP and OXT, reaching from acute regulation of the respective social behaviour to the long-term modulation of related behaviours including anxiety and social cognition. In conclusion, measuring the in vivo release patterns of AVP and OXT within distinct brain regions during the display of diverse social behaviours and manipulation of local AVP and OXT activity has yielded new insights into the specific roles of these neuropeptides in the regulation of complex social behaviours.
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Review
The age of plasticity: developmental regulation of synaptic plasticity in neocortical microcircuits.
Proper wiring of neural circuits during development depends on both molecular cues that guide connectivity and activity-dependent mechanisms that use patterned activation to adjust the strength and number of synaptic connections. In this chapter, we discuss some of the plasticity mechanisms underlying the experience-dependent rewiring of visual cortical microcircuits focusing on layer 4 of rat primary visual cortex. The microcircuit in layer 4 has the ability to regulate its excitability by shifting the balance between excitatory and inhibitory synaptic transmission in an experience-dependent manner. ⋯ In contrast, during the classical sensitive period for rodent visual system plasticity, this homeostatic response is replaced by mechanisms that reduce the responsiveness of deprived cortex. We discuss this developmentally regulated switch in plasticity within layer 4 and how this might depend on the maturation of excitatory and inhibitory monosynaptic connections. Based on our published data, we propose inhibitory plasticity as an important player in circuit refinement that can contribute both to the compensatory forms of circuit plasticity in the early stages of development and to the pathological loss of function induced by visual deprivation during the critical period.
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Synaptic plasticity has often been argued to play an important role in learning and memory. The discovery of long-term potentiation (LTP) and long-term depression (LTD), the two most widely cited cellular models of synaptic plasticity, significantly spurred research in this field. ⋯ In this review, we discuss a number of recent advancements in the understanding of the mechanisms that mediate LTP and LTD in the rodent hippocampus and focus on the use of subunit-specific N-methyl-d-aspartate receptor antagonists and interference peptides as potential tools to study the role of synaptic plasticity in learning and memory. By using the modulation of synaptic plasticity and hippocampal-dependent learning and memory by acute stress as an example, we review a large body of convincing evidence indicating that alterations in synaptic plasticity underlie the changes in learning and memory produced by acute stress.