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PubMed2001

Influence of postweaning social isolation in the rat on brain development, conditioned behaviour and neurotransmission.

There is substantial evidence that early life events influence brain development and subsequent adult behaviour and play an important role in the causation of certain psychiatric disorders including schizophrenia and depression. The underlying mechanism of the effects of these early environmental factors is still not understood. It is a challenge to attempt to model early environmental factors in animals to gain understanding of the basic mechanisms that underlie the long-term effects. This paper reviews the effects of rearing rats from weaning in social isolation and reports some recent results indicating hippocampal dysfunction. Isolation rearing in rats from weaning produces a range of persistent behavioural changes in the young adult, including hyperactivity in response to novelty and amphetamine and altered responses to conditioning. These are associated with alterations in the central aminergic neurotransmitter functions in the mesolimbic areas and other brain regions. Isolation-reared rats have enhanced presynaptic dopamine (DA) and 5-HT function in the nucleus accimbens (NAC) associated with decreased presynaptic 5-HT function in the frontal cortex and hippocampus. Isolation-reared rats have reduced presynaptic noradrenergic function in the hippocampus, but have enhanced presynaptic DA function in the amygdala. These neurochemical imbalances may contribute to the exaggerated response of the isolated rat to a novel stimulus or to stimuli predictive of danger, and isolation-induced behavioural changes. These changes have neuroanatomical correlates; changes which seem to parallel to a certain degree those seen in human schizophrenia. A greater understanding of the processes that underlie these changes should improve our knowledge of how environmental events may alter brain development and function, and play a role in the development of neuropsychiatric disorders.

Animals↗
PubMed2003

Influence of postweaning social isolation in the rat on brain development, conditioned behavior, and neurotransmission.

There is substantial evidence that early life events influence brain development and subsequent adult behavior and play an important role in the causation of certain psychiatric disorders including schizophrenia and depression. The underlying mechanism of the effects of these early environmental factors is still not understood. It is a challenge to attempt to model early environmental factors in animals to gain understanding of the basic mechanisms that underlie the long-term effects. This paper reviews the effects of rearing rats from weaning in social isolation and reports some recent results indicating hippocampal dysfunction. Isolation rearing in rats from weaning produces a range of persistent behavioral changes in the young adult, including hyperactivity in response to novelty and amphetamine and altered responses to conditioning. These are associated with alterations in the central aminergic neurotransmitter functions in the mesolimbic areas and other brain regions. Isolation-reared rats have enhanced presynaptic dopamine (DA) and 5-HT function in the nucleus accumbens (NAC) associated with decreased presynaptic 5-HT function in the frontal cortex and hippocampus. Isolation-reared rats have reduced presynaptic noradrenergic function in the hippocampus, but have enhanced presynaptic DA function in the amygdala. These neurochemical imbalances may contribute to the exaggerated response of the isolated rat to a novel stimulus or to stimuli predictive of danger, and isolation-induced behavioral changes. These changes have neuroanatomical correlates, changes which seem to parallel to a certain degree those seen in human schizophrenia. A greater understanding of the processes that underlie these changes should improve our knowledge of how environmental events may alter brain development and function, and play a role in the development of neuropsychiatric disorders.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Effects of social isolation rearing on learning in the Morris water maze.

Impaired learning has been shown as a consequence of isolation-rearing in a variety of paradigms. However, there are situations in which learning in isolation-reared rats is enhanced or unimpaired compared to socially reared rats. The present experiments investigated the effects of isolation rearing on place navigation in the Morris water maze. Two complementary paradigms were studied: isolation and socially reared rats were exposed to the water maze either without drug pretreatment or following systemic administration of scopolamine. Two conditions were examined: place learning and reversal learning. Male Lister hooded rats were either housed singly (isolation reared) or in groups of four (social reared) from weaning at 21 days of age. Six weeks later place learning and reversal learning were determined using the Morris water maze. The time taken to locate the submerged island (escape latency) was used as the measure of learning ability. The results showed that place learning, and reversal learning were enhanced in isolation reared rats compared to socially reared controls. Pretreatment with scopolamine (0.3 and 0.5 mg/kg, i.p.) produced a dose-related cognitive deficit as shown by an increase in the escape latency. Scopolamine (0.3 mg/kg) impaired both place and reversal learning but this was less pronounced in isolation compared to socially-reared rats. These results suggest that rearing in isolation may enhance spatial learning though central cholinergic mechanisms.

Animals↗
PubMed2006

The effects of social isolation on neuropeptide Y levels, exploratory and anxiety-related behaviors in rats.

NPY is one of the most abundantly expressed peptides within the CNS, and has been previously demonstrated to be altered in several animal models of depression, as well as to be differentially regulated by acute and repeated stress. The effect of social deprivation, through isolation housing, on brain NPY concentrations in adult rats has not been previously investigated. The effects of 12 weeks of social isolation, in adult rats, on anxiety-related behaviors and central concentrations of NPY in: hypothalamus, amygdala, caudate-putamen, hippocampus, and frontal cortex were evaluated. Single housed animals spent significantly more time on the open arms of the elevated plus maze and in the central area of the open field as compared to pair housed controls. These data are most likely indicative of enhanced exploration and novelty seeking. Concentrations of neuropeptide Y were increased in the caudate-putamen of the single housed subjects. NPY levels in caudate/putamen and hypothalamus were also significantly correlated with time spent in the open arms of the elevated plus maze. These data suggest that chronic social isolation, in these adult Wistar rats, did not increase anxiety but produced enhanced exploration in tests of anxiety, an effect that was associated with NPY concentrations in the striatum and hypothalamus.

Animals↗
PubMed1990

Increased sensitivity to amphetamine and reward-related stimuli following social isolation in rats: possible disruption of dopamine-dependent mechanisms of the nucleus accumbens.

These experiments compared isolation-reared and socially-reared rats in two complementary paradigms for measuring responding to signals of reward, both undrugged and following either systemic or intraaccumbens d-amphetamine (AMPH). In experiment 1, locomotor activity conditioned to food presentation was measured in rats exposed to a restricted feeding schedule. The interaction between this conditioned activity, AMPH administration (0.5, 2.0, 3.5, 5.0 mg/kg IP) and motivational state was measured. In experiment 2, hungry rats were trained to associate a compound light/noise stimulus with sucrose reward and were then implanted with guide cannulae in the nucleus accumbens. In the test phase, responding on one of two novel levers produced the compound stimulus (conditioned reinforcer; CR). Responses on the other lever had no effect. Each rat received four counterbalanced intra-accumbens infusions of AMPH (0, 3, 10, 20 micrograms). In both experiments, isolated rats responded more with stimuli associated with reward and this differential rearing effect was further exaggerated by AMPH. The isolation-induced sensitivity to these stimuli and to AMPH was critically dependent on motivational variables. Thus, in experiment 1 there were no differences between the groups when sated or during extinction and in experiment 2 the increased responding was restricted to the lever providing CR. Measurements of the locomotor response to intra-accumbens AMPH (0, 3, 10 micrograms) also revealed that isolated rats were more sensitive to a low dose of the drug when tested food-deprived in a relatively novel environment. These results suggest that the experience of isolation-rearing interacts either directly or indirectly with dopamine-dependent mechanisms of the nucleus accumbens to enhance the effects of reward-related stimuli.

Animals↗
PubMedDate not supplied

Influence of social isolation and 6-OHDA lesion on the effects of quinelorane.

The sensitivity of the response to the preferential dopaminergic D3 (DAD3) receptor agonist, quinelorane, was compared in mice housed socially and in mice isolated for 4 weeks. Quinelorane (1, 5, 10, 50 and 100 microg/kg) was administered intraperitoneally. Motor activity was measured for 60 min posttreatment. Rectal temperature was measured prior to and 1 h following the administration of quinelorane (10, 50 and 100 microg/kg i.p.). Quinelorane significantly and dose-dependently decreased locomotor activity in social and in isolated mice. The locomotor activity of isolated mice was significantly lower than that of social mice, but isolation had no effect on quinelorane-induced hypomotility. Quinelorane decreased dose-dependently rectal temperature in isolated and social mice, but isolation had no effect on quinelorane-induced decrease in rectal temperature. The lesions of dopaminergic terminals with intracerebroventricular administration of 6-OHDA decreased the dopamine (DA) level by 93% in the nucleus accumbens and by 91% in the corpus striatum; these lesions impaired neither the hypolocomotion nor the hypothermia induced by quinelorane. Thus, it may be concluded that social isolation has no influence on the quinelorane-induced decreases in rectal temperature and in locomotor activity and that the DA receptors involved in these effects of quinelorane are located postsynaptically.

Animals↗
PubMed2001

Implications of social isolation during cancer treatment. The implications of residence away from home during cancer treatment on patients' experiences: a comparative study.

With the centralisation and specialisation of cancer services, patients may have to travel considerable distances and stay away from their homes during treatment. This paper describes a comparative study that sought to identify the effects on patients of receiving chemotherapy and/or radiotherapy away from their homes, families and social support networks. Eighty four cancer patients treated in Southampton (42 from Guernsey and 42 from Southampton) agreed to participate in a structured interview and a standardised measure of social support. There were few differences in terms of satisfaction with services between Guernsey patients who stayed away from home during treatment and Southampton patients who lived at home. Counter-intuitively, Guernsey patients perceived themselves to have better social support.

Adult↗