Chronic imipramine treatment partially reverses the long-term changes of hippocampal synaptic plasticity in socially stressed rats.

In the present study, we investigated whether synaptic plasticity changes in the hippocampus of depressive-like socially stressed rats could be reversed by chronic antidepressant treatment. To that end, rats were either defeated and subsequently individually housed or subjected to control treatment followed by social housing. After a period of at least 3 months, rats were either treated chronically with imipramine (20 mg/kg per day, per os for at least 3 months) or the solvent solution (i.e. water). Then, long-term potentiation and depression were measured in the CA1 region of the hippocampus in vitro. Chronic imipramine treatment partially restored the attenuated induction of long-term potentiation and suppressed the facilitation of long-term depression-induction in socially stressed rats. The altered synaptic plasticity after social stress is discussed in relation to cognitive deficits and hippocampal changes that are observed in depressive patients.

Long-term impairment of social memory in the rat after social defeat is not restored by desglycinamide-vasopressin.

Repeated social defeat followed by individual housing caused a long-term impairment of social memory in male rats. Social memory, as assessed in the social discrimination test using an intertrial interval of 3 min, was impaired for at least 8 weeks after the social defeat experience. Since social memory of male rodents depends on proper functioning of the sexually dimorphic vasopressin system, it was investigated whether a centrally active vasopressin fragment could restore the impaired social memory. Subcutaneous administration of 6 microg/kg of the vasopressin fragment desglycinamide-vasopressin (VP1-8) 40 days after social defeat slightly improved social memory in both control and socially defeated rats. It is concluded that social defeat followed by individual housing caused a long-term impairment of social memory, which was not restored by treatment with VP1-8.

Delayed effect of the vasopressin metabolite VP4-8 on the social memory of sexually naive male rats.

RATIONALE: Endogenous vasopressin is involved in the social memory of the male rat and administration of exogenous vasopressin improves social memory. These findings are mainly based on studies using sexually experienced males that were tested in the social recognition test. OBJECTIVE: The present study was aimed to establish whether the modulation of social memory by vasopressin fragments depends on the sexual experience of the male rat. For this purpose, the social discrimination test was used, since this test is more suitable than the social recognition test for measuring social memory in sexually naive males. METHODS: Male rats were tested in the social discrimination test and treated subcutaneously with the vasopressin metabolite [pGlu4,Cyt6]vasopressin-(4-8) (VP4-8). VP4-8 shares with vasopressin the effects on memory processes but lacks the peripheral effects of vasopressin. RESULTS: VP4-8 (1 microgram/kg) acutely improved the social memory of sexually experienced male rats, confirming previous reports. However, in sexually naive males VP4-8 failed to improve social memory in doses ranging from 0.1 microgram/kg to 1 microgram/kg. Instead, 1 microgram/kg VP4-8 or 6 micrograms/kg desglycinamide-vasopressin were found to exert a delayed effect in sexually naive rats. This delayed effect resulted in an improved social memory 2 days after administration. CONCLUSIONS: Vasopressin sensitisation is discussed as a possible underlying mechanism of the observed delayed effect of vasopressin fragments. It is concluded that in male rats sexual experience can influence the modulation of social memory by vasopressin.

Social memory in the rat: circadian variation and effect of circadian rhythm disruption.

Disruption of circadian rhythm can impair long-term passive avoidance memory of rats and mice. The present study investigated whether disruption of circadian rhythm can also impair social memory of male rats. Social memory was assessed using the social discrimination test, in which a short-term olfactory memory is formed by social interaction with a juvenile rat during a learning trial. After an intertrial interval, a retrieval trial is performed, in which social memory is expressed as a decreased attention paid to the same juvenile as compared to a new juvenile. First, the social memory at four different time points across the light-dark cycle was measured with an intertrial interval of 10 or 25 min. There was no significant circadian variation of social memory across the light-dark cycle. Subsequently, the effect of a -6 or 12-h phase shift on social memory was studied. These phase shifts were previously found to impair long-term passive avoidance memory. However, no effect of either phase shift was observed in the social discrimination test. It is concluded that the disruption of circadian rhythm had no effect on the social memory of rats. Differences between short-term social memory and long-term passive avoidance memory are discussed in relation to their apparent differential susceptibility to the effects of circadian rhythm disruption.

Defeat followed by individual housing results in long-term impaired reward- and cognition-related behaviours in rats.

In contrast to the well-documented acute effects on behavioural sensitivity, chronic effects that persist for weeks or even months after the cessation of the stressor received relatively little attention. This study aimed at the long-term effects of a severe stressor, i.e. social defeat followed by individual housing. Defeated and subsequently individually housed animals displayed impaired social memory, decreased social interaction and diminished anticipation for a sucrose solution for up until a period of 3 months after defeat. Remarkably, social housing counteracted the defeat-induced effects. The impaired capability to anticipate for a reward was discussed in relation to anhedonia, an important symptom of human depression. Moreover, the disturbed memory, the chronic nature of the effects, and the therapeutic effects of social housing, suggest that the defeat model may serve as a potential model for human psychopathology.

Differential responses of phosphorylated mitogen-activated protein kinase and phosphorylated cyclic-AMP response element-binding protein immunoreactivity in the rat brain to sub-convulsive pentylenetetrazol.

The possible advantage of using multiple phospho-specific antibodies to study changes in brain activity was assessed. For this purpose, rats were injected intraperitoneally with either a control treatment or 15 mg/kg pentylenetetrazol. The sub-convulsive dose of pentylenetetrazol did not induce marked behavioural effects. Ten minutes after treatment, the rats were perfused and the brains were dissected. Adjacent brain sections were immunohistochemically stained for phosphorylated cyclic-AMP response element-binding protein and phosphorylated mitogen-activated protein kinase. Opposite effects of pentylenetetrazol treatment were observed on the immunoreactivity of these two antibodies within the hypothalamic paraventricular nucleus, the supraoptic nucleus and the arcuate nucleus. In these regions, pentylenetetrazol treatment increased phosphorylated mitogen-activated protein kinase immunoreactivity, but decreased phosphorylated cyclic-AMP response element-binding protein immunoreactivity. These findings show that changes in the activity of a brain nucleus can be accompanied by differential changes in the activity of two signal transduction pathways, which can be detected immunohistochemically. Therefore, the use of multiple phospho-specific antibodies may enhance our potential to monitor changes in brain activity.

Vasopressin metabolites: a link between vasopressin and memory?

The effects of endogenous metabolites of the neuropeptide vasopressin (VP) in behavioural tests led to the hypothesis that VP metabolites have a more selective function than VP. In contrast to VP, no peripheral effects have been found thus far with VP metabolites and their function seems to be associated with memory-related behaviour. VP metabolites can improve both consolidation and retrieval of memory. Effects on autonomic and electrophysiological parameters and interactions with other neurotransmitter systems have provided some information about the processes that could underlie the effects of VP metabolites on memory-related behaviour. There is evidence that the effects of VP metabolites could be mediated by a VP metabolite receptor, which is different from the known VP receptors. The VP metabolite receptor could be a link between the neuropeptide VP and memory-related behaviour.

Changes in prepulse inhibition after local administration of NMDA receptor ligands in the core region of the rat nucleus accumbens.

The dopamine and glutamate hypotheses are two pharmacological models for schizophrenia. In the present investigations, the prepulse inhibition paradigm was used to evaluate the role of the nucleus accumbens core region in both models. Prepulse inhibition is known to be decreased in schizophrenics, when compared with control patients, and in rats after systemic injection of dopamine receptor agonists and non-competitive antagonists of the NMDA receptor. In the present study injection of dopamine in the rat nucleus accumbens core region also decreased prepulse inhibition. Injections of NMDA decreased, whereas a low dose of the competitive NMDA receptor antagonist (+/-)-2-amino-5-phosphonopentanoic acid (AP-5) and the non-competitive NMDA receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydroxy-5H-dibenzo[a,d]cyclohepten-5 ,10-imine hydrogen maleate (MK-801) increased prepulse inhibition. The results indicate an involvement of the accumbens core in mediating the systemic effects on prepulse inhibition of dopamine receptor agonists but not of non-competitive NMDA receptor antagonists.

Effects of acoustic prepulses on the startle reflex in rats: a parametric analysis.

Small changes in the sensory environment, called prepulses, prior to a startle-eliciting stimulus can either inhibit or facilitate the startle reaction. To investigate this apparent discrepancy, a number of characteristics of the acoustic prepulse were varied and the effects on the startle reaction were studied. The results showed that increasing the intensity of the prepulse (81-85 dB) resulted in an increased inhibition and could even turn facilitation into inhibition (at 3-13 ms prepulse-startle interval). Varying prepulse lengths (1-45 ms) did not change the observed startle modification. Only when the prepulse offset was close to the startle onset, changes could be observed. Confronting the animal with the same test session for several days resulted in increased inhibition and a change from facilitation to inhibition (at 3-13 ms prepulse-startle interval). The results demonstrate that the characteristics of the prepulse determine its effect on the startle reaction. An hypothetical model is proposed which might explain the observed data.

Effects of acoustic prepulses on the startle reflex in rats: a parametric analysis.

Small changes in the sensory environment, called prepulses, prior to a startle-eliciting stimulus can either inhibit or facilitate the startle reaction. To investigate this apparent discrepancy, a number of characteristics of the acoustic prepulse were varied and the effects on the startle reaction were studied. The results showed that increasing the intensity of the prepulse (81-85 dB) resulted in an increased inhibition and could even turn facilitation into inhibition (at 3-13 ms prepulse-startle interval). Varying prepulse lengths (1-45 ms) did not change the observed startle modification. Only when the prepulse offset was close to the startle onset, changes could be observed. Confronting the animal with the same test session for several days resulted in increased inhibition and a change from facilitation to inhibition (at 3-13 ms prepulse-startle interval). The results demonstrate that the characteristics of the prepulse determine its effect on the startle reaction. An hypothetical model is proposed which might explain the observed data.

Acoustic prepulses can facilitate the startle reflex in rats: discrepancy between rat and human data resolved.

Small changes in the sensory environment, called prepulses, prior to a startle-eliciting stimulus can inhibit or facilitate the startle reaction. Previous studies reported that at large intervals between prepulse and startle stimulus the prepulse facilitates the startle reaction, possibly by means of an orienting response. This was, however, only observed in humans and not in rats, and was consequently proposed to measure unique brain functions. In the present study with rats, the prepulse intensity was decreased from 85 to 81 dB, which resulted in decreased prepulse inhibition. Prepulse facilitation was now observed at large intervals (> 800 ms), which suggests that this facilitation was masked by inhibition in previous studies. These results solve the discrepancy between rat and human data and indicate that similar mechanisms are involved.