The Novel Analogue of Modafinil CE-158 Protects Social Memory against Interference and Triggers the Release of Dopamine in the Nucleus Accumbens of Mice.

Previous studies have shown that atypical dopamine-transporter-inhibitors such as modafinil and its analogues modify behavioral and cognitive functions in rodents. Here, we tested potential promnestic effects of the novel, more dopamine-transporter selective modafinil analogue CE-158 in the social discrimination memory task in male mice. Systemic administration of CE-158 1 h before the social learning event prevented the impairment of social-recognition memory following retroactive interference 3 h after the learning session of a juvenile conspecific.

Rescue of Vasopressin Synthesis in Magnocellular Neurons of the Supraoptic Nucleus Normalises Acute Stress-Induced Adrenocorticotropin Secretion and Unmasks an Effect on Social Behaviour in Male Vasopressin-Deficient Brattleboro Rats.

The relevance of vasopressin (AVP) of magnocellular origin to the regulation of the endocrine stress axis and related behaviour is still under discussion. We aimed to obtain deeper insight into this process. To rescue magnocellular AVP synthesis, a vasopressin-containing adeno-associated virus vector (AVP-AAV) was injected into the supraoptic nucleus (SON) of AVP-deficient Brattleboro rats (di/di).

Vasopressin and post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with a wide range of behavioral disturbances and serious consequences for both patient and society. One of the main reasons for unsuccessful therapies is insufficient knowledge about its underlying pathomechanism. In the search for centrally signaling molecules that might be relevant to the development of PTSD we focus here on arginine vasopressin (AVP).

Differential Effects of Novel Dopamine Reuptake Inhibitors on Interference With Long-Term Social Memory in Mice.

In the laboratory, long-term social recognition memory (SRM) in mice is highly susceptible to proactive and retroactive interference. Here, we investigate the ability of novel designed dopamine (DA) re-uptake inhibitors (-CE-123 and -CE-123) to block retroactive and proactive interference, respectively. Our data show that administration of -CE-123 30 min before learning blocks retroactive interference that has been experimentally induced at 3 h, but not at 6 h, post-learning.

Vasopressinergic control of stress-related behavior: studies in Brattleboro rats.

Vasopressin, a nonapeptide, signaling both as hormone in the blood and neuromodulator/neurotransmitter in the brain is considered to be causally involved in the pathological changes underlying anxiety and depression. In the present review we summarize experimental data obtained with Brattleboro rats as a model of congenital vasopressin-deficiency to test the hypothesis that central vasopressin signaling contributes to anxiety- and depression-like behavior. Male, female and lactating rats were studied.

Recognizing Others: Rodent's Social Memories.

We provide in this chapter a brief overview of the present knowledge about social memory in laboratory rodents with a focus on mice and rats. We discuss in the first part the relevance of the processing of olfactory cues for social recognition in these animals and present information about the brain areas involved in the generation of a long-term social memory including cellular mechanisms thought to underlie memory consolidation. In the second part, we suggest that sensory modalities beyond olfaction may also be important in contributing to the long-term social memory trace including audition and taction (and vision).

Vasopressin signaling at brain level controls stress hormone release: the vasopressin-deficient Brattleboro rat as a model.

The nonapeptide arginine vasopressin (AVP) has long been suggested to play an important role as a secretagogue for triggering the activity of the endocrine stress response. Most recent studies employed mutant mice for analyzing the importance of AVP for endocrine regulation under stress. However, it is difficult to compare and draw overall conclusions from all these studies as mixing the genetic material from different mouse strains has consequences on the individual's stress response.

Consequences of temporary inhibition of the medial amygdala on social recognition memory performance in mice.

Different lines of investigation suggest that the medial amygdala is causally involved in the processing of information linked to social behavior in rodents. Here we investigated the consequences of temporary inhibition of the medial amygdala by bilateral injections of lidocaine on long-term social recognition memory as tested in the social discrimination task. Lidocaine or control NaCl solution was infused immediately before learning or before retrieval.

Timing of presentation and nature of stimuli determine retroactive interference with social recognition memory in mice.

The present study was designed to further investigate the nature of stimuli and the timing of their presentation, which can induce retroactive interference with social recognition memory in mice. In accordance with our previous observations, confrontation with an unfamiliar conspecific juvenile 3h and 6h, but not 22 h, after the initial learning session resulted in retroactive interference. The same effect was observed with the exposure to both enantiomers of the monomolecular odour carvone, and with a novel object.

Restoration of peripheral V2 receptor vasopressin signaling fails to correct behavioral changes in Brattleboro rats.

Beside its hormonal function in salt and water homeostasis, vasopressin released into distinct brain areas plays a crucial role in stress-related behavior resulting in the enhancement of an anxious/depressive-like state. We aimed to investigate whether correction of the peripheral symptoms of congenital absence of AVP also corrects the behavioral alterations in AVP-deficient Brattleboro rats. Wild type (WT) and vasopressin-deficient (KO) male Brattleboro rats were tested.

Blunted HPA axis response in lactating, vasopressin-deficient Brattleboro rats.

Adaptation to stress is a basic phenomenon in mammalian life that is mandatorily associated with the activity of the hypothalamic-pituitary-adrenal (HPA) axis. An increased resting activity of the HPA axis can be measured during pregnancy and lactation, suggesting that these reproductive states lead to chronic load in females. In this study, we examined the consequences of the congenital lack of vasopressin on the activity of the HPA axis during lactation using vasopressin-deficient Brattleboro rats.

Social investigation and long-term recognition memory performance in 129S1/SvImJ and C57BL/6JOlaHsd mice and their hybrids.

When tested for their behavioural performance, the mixed genetic background of transgenic mice is a critical, but often ignored, issue. Such issues can arise because of the significant differences in defined behavioural parameters between embryonic stem cell donor and recipient strains. In this context, the commonly used stem cell donor strain '129' shows 'deficits' in different paradigms for learning and long-term memory.

Testing declarative memory in laboratory rats and mice using the nonconditioned social discrimination procedure.

Testing declarative memory in laboratory rodents can provide insights into the fundamental mechanisms underlying this type of learning and memory processing, and these insights are likely to be applicable to humans. Here we provide a detailed description of the social discrimination procedure used to investigate recognition memory in rats and mice, as established during the last 20 years in our laboratory. The test is based on the use of olfactory signals for social communication in rodents; this involves a direct encounter between conspecifics, during which the investigatory behavior of the experimental subject serves as an index for learning and memory performance.

Vasopressin and social odor processing in the olfactory bulb and anterior olfactory nucleus.

Central vasopressin facilitates social recognition and modulates numerous complex social behaviors in mammals, including parental behavior, aggression, affiliation, and pair-bonding. In rodents, social interactions are primarily mediated by the exchange of olfactory information, and there is evidence that vasopressin signaling is important in brain areas where olfactory information is processed. We recently discovered populations of vasopressin neurons in the main and accessory olfactory bulbs and anterior olfactory nucleus that are involved in the processing of social odor cues.

Expression of early growth response protein 1 in vasopressin neurones of the rat anterior olfactory nucleus following social odour exposure.

The anterior olfactory nucleus (AON), a component of the main olfactory system, is a cortical region that processes olfactory information and acts as a relay between the main olfactory bulbs and higher brain regions such as the piriform cortex. Utilizing a transgenic rat in which an enhanced green fluorescent protein reporter gene is expressed in vasopressin neurones (eGFP-vasopressin), we have discovered a population of vasopressin neurones in the AON. These vasopressin neurones co-express vasopressin V1 receptors.

Different importance of the volatile and non-volatile fractions of an olfactory signature for individual social recognition in rats versus mice and short-term versus long-term memory.

When tested in the olfactory cued social recognition/discrimination test, rats and mice differ in their retention of a recognition memory for a previously encountered conspecific juvenile: Rats are able to recognize a given juvenile for approximately 45 min only whereas mice show not only short-term, but also long-term recognition memory (≥ 24 h). Here we modified the social recognition/social discrimination procedure to investigate the neurobiological mechanism(s) underlying the species differences. We presented a conspecific juvenile repeatedly to the experimental subjects and monitored the investigation duration as a measure for recognition.

An intrinsic vasopressin system in the olfactory bulb is involved in social recognition.

Many peptides, when released as chemical messengers within the brain, have powerful influences on complex behaviours. Most strikingly, vasopressin and oxytocin, once thought of as circulating hormones whose actions were confined to peripheral organs, are now known to be released in the brain, where they have fundamentally important roles in social behaviours. In humans, disruptions of these peptide systems have been linked to several neurobehavioural disorders, including Prader-Willi syndrome, affective disorders and obsessive-compulsive disorder, and polymorphisms of V1a vasopressin receptor have been linked to autism.

Urocortin 1 administered into the hypothalamic supraoptic nucleus affects open-field behaviour in rats.

The presence of both Urocortin 1 (Ucn1) and corticotropin-releasing factor 2 receptors (CRF(2)R) in the hypothalamic supraoptic nucleus (SON) suggests that endogenous Ucn1 released within this brain area acts as a local signal that might be involved in the regulation of not only endocrine but also behavioural stress responses. To test this hypothesis, we monitored the effects induced by the administration of a range of doses of synthetic Ucn1 (0.001-1.

High-resolution mapping of neuronal activity using the lipophilic thallium chelate complex TlDDC: protocol and validation of the method.

In neurons the rate of K(+)-uptake increases with increasing activity. K(+)-analogues like the heavy metal ion thallium (Tl(+)) can be used, therefore, as tracers for imaging neuronal activity. However, when water-soluble Tl(+)-salts are injected systemically only minute amounts of the tracer enter the brain and the Tl(+)-uptake patterns are influenced by regional differences in blood-brain barrier (BBB) K(+)-permeability.

Congenital lack of nNOS impairs long-term social recognition memory and alters the olfactory bulb proteome.

The gaseous neurotransmitter nitric oxide (NO), synthesized by the enzyme neuronal nitric oxide synthase (nNOS), is thought to play a major role in the modulation of memory. We tested adult nNOS-deficient and wild-type mice for their recognition memory abilities in the social discrimination paradigm, which is based on olfactory cues. Subsequently, proteomic investigation of the olfactory bulbs of both genotypes were performed under basal conditions and 6 h after learning, i.

Vasopressin administration into the paraventricular nucleus normalizes plasma oxytocin and corticosterone levels in Brattleboro rats.

Adult male rats of the Brattleboro strain were used to investigate the impact of the congenital absence of vasopressin on plasma adrenocorticotropin, corticosterone, and oxytocin concentrations as well as the release pattern of oxytocin within the hypothalamic paraventricular nucleus (PVN), in response to a 10-min forced swimming session. Measurement of adrenocorticotropin in plasma samples collected via chronically implanted jugular venous catheters revealed virtually identical stress responses for vasopressin-lacking Brattleboro (KO) and intact control animals. In contrast, plasma corticosterone and oxytocin levels were found to be significantly elevated 105 min after onset of the stressor in KO animals only.

Response of the adrenomedullary system to early postnatal stress in the Brattleboro rat.

The sympathetic-adrenomedullary system and the pituitary-adrenocortical axis are linked to each other by chemical signals transferring information between both endocrine systems. Here we addressed the question of whether the neuropeptide arginine vasopressin (AVP) is involved in this type of information transfer during early postnatal development. The impact of congenital absence of AVP on the endocrine stress response was investigated using the AVP-deficient Brattleboro rat.

Competition between two memory traces for long-term recognition memory.

Previous studies investigating the processes which underlie memory consolidation focused almost exclusively on isolated learning events. Here I studied the competition of two similar memory traces for consolidation non-conditioned recognition memory in adult male C57BL/6JOlaHsd mice using the olfactory cues based social discrimination procedure. My results show that the interference phenomena that cause forgetting are time-dependent, and that retroactive interference can be discriminated from proactive interference.

Vasopressin in the septum: not important versus causally involved in learning and memory--two faces of the same coin?

Intraseptal arginine vasopressin (AVP) has been suggested to control in laboratory rodents not only emotionality but also learning and memory. However, depending upon the nature of the test procedure and, thus, the specific memory paradigm under study, administration of synthetic AVP into the lateral septum can have no effect, enhance or even impair learning and memory. Similar contradictory results were obtained after local administration of AVP V1 receptor antagonists in different learning and memory paradigms: blockade of AVP signalling in the lateral septum revealed either no essential function or a significant contribution of the endogenous neuropeptide.

Listening to neuropeptides by microdialysis: echoes and new sounds?

Neuropeptides represent the largest class of neuromessengers in the central nervous system. They are involved in the regulation of growth processes, reproduction, social behavior, emotion/motivation and cognition. Particularly in subcortical structures, neuropeptides act as neuromodulators, which reach their target sites via diffusion through the extracellular space.