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Biomedical subjects

F S Hall

Publications and source records attributed to F S Hall.

36 records · Page 2Linked to original sources

Effects of isolation-rearing on locomotion, anxiety and responses to ethanol in Fawn Hooded and Wistar rats.

Voluntary ethanol (EtOH) consumption is increased by isolation-rearing in several rat strains. The following experiments examined the effects of isolation-rearing on basal and ethanol-stimulated behavior in Fawn Hooded rats, an alcohol-preferring rat strain, compared to Wistar rats. Locomotor activity and anxiety were examined under both conditions. Basal locomotor activity was higher in isolated subjects of both strains in low light conditions, but under bright light conditions, this difference was only observed in Wistar rats. Locomotor stimulant effects of EtOH were only observed in isolation-reared rats. In the elevated plus maze, Fawn Hooded rats were more anxious than Wistar rats under low light conditions, but under bright light conditions, Wistar socials were less anxious than all of the other groups. Administration of 1.5 mg/kg EtOH produced an anxiolytic response in the elevated plus maze under bright light conditions in Fawn Hooded rats, but to a lesser degree Wistar rats, particularly Wistar isolates. In conclusion, although both strain and isolation-rearing had effects on locomotion and anxiety as well as the stimulatory and anxiolytic effects of EtOH, these effects appeared to be independent.

Animals↗

Effects of isolation-rearing on voluntary consumption of ethanol, sucrose and saccharin solutions in Fawn Hooded and Wistar rats.

These experiments examined the hypothesis that isolation-rearing and strain influence hedonic mechanisms. In experiment 1, voluntary consumption of ethanol and water was monitored in the home cage of Fawn Hooded (FH) and Wistar rats. FH rats were found to consume more ethanol at low concentrations than Wistar rats, independent of rearing condition, and isolation-reared rats were found to consume more of high ethanol concentrations, independent of strain. In experiment 2, isolation-reared rats were found to consume more sucrose, independent of concentration, than socially reared rats. In experiment 3, Fawn Hooded rats were found to be more sensitive to low concentration solutions of saccharin, and to consume less of the high concentration solutions, while isolation-rearing was found to enhance consumption of high concentrations. Thus, hedonic processes are independently modulated by strain and rearing conditions, although the effects of isolation-rearing appear to be exacerbated in Fawn Hooded rats.

Alcohol Drinking↗

Isolation rearing in rats: pre- and postsynaptic changes in striatal dopaminergic systems.

Isolation rearing of rats produces a behavioral syndrome indicative of altered dopamine (DA) function in the nucleus accumbens (NAC). The present experiments extend these findings by investigating: (a) interactions between isolation rearing and repeated handling/testing on presynaptic DA function in the NAC using in vivo microdialysis: (b) the dose-response curve for the effects of d-amphetamine, and the responses elicited by high potassium, using in vivo microdialysis, and (c) postsynaptic function in isolates as indexed by DA receptor-linked cAMP production. Experiment 1 showed that both isolation rearing and repeated handling/testing had effects on monoamine function in the NAC. However, while both manipulations enhanced DA release evoked by d-amphetamine, only isolated rats had elevated basal DA levels. Opposite neurochemical changes were observed with respect to the serotonin metabolite 5-HIAA, isolates having lower, and repeatedly handled/tested animals having higher, extracellular levels. Experiment 2 provided evidence for enhanced d-amphetamine-evoked DA release in isolated animals, while potassium-evoked DA release was reduced. Experiment 3 provided evidence that the isolation rearing induced changes in presynaptic DA function were accompanied by postsynaptic changes. Specifically, the inhibitory influence of the D2 receptor on D1 receptor-stimulated cAMP production was attenuated in ventral striatal slices taken from isolates, suggesting a functional downregulation of D2 receptors.

Animals↗

Social deprivation of neonatal, adolescent, and adult rats has distinct neurochemical and behavioral consequences.

This review examines the consequences of social deprivation on brain chemistry and behavior on rats. Although social deprivation produces wide-ranging behavioral and neurochemical effects, it appears that these effects are determined by a number of factors, the most critical factor being the age or developmental stage during the period of deprivation. Roughly, the effects examined in this review may be separated into three major developmental stages and each is related to deprivation of specific types of social interaction: preweaning/neonatal, postweaning/adolescent, and adult. The effects of social deprivation during each of these stages appears to be neurochemically and behaviorally specific. However, much of the research to date has failed to examine deprivation during specific stages, often combining deprivation of different types. Nonetheless, these modifications of experience produce animals of differing phenotypes, which could be characterized as pathological in nature in many instances, and may model particular aspects of human psychopathologies or perhaps the propensity to develop those phenotypic features.

Age Factors↗

The effects of isolation-rearing of rats on behavioural responses to food and environmental novelty.

Isolation-reared rats exhibited enhanced behavioural responses to novelty, but only some aspects of such behavior was affected. In Experiment 1, environmental neophobia was enhanced but food neophobia was diminished in isolation-reared rats compared to socially reared rats. However, in Experiment 2, when subjects were not handled extensively prior to testing, no differences in behavioural responses to environmental or food novelty in an open-field were observed between rearing groups. The difference between these experiments was hypothesized to be the result of ceiling effects produced by increased anxiety or arousal in experiment 2 in which the animals had not been extensively handled. In summary, in these experiments anticipatory responses to novelty were alterred by isolation-rearing but the behavioural expression of this increased sensitivity was determined by intrinsic aversive/rewarding or arousing qualities of novel environments and novel foods.

Animals↗

The effects of isolation-rearing on sucrose consumption in rats.

Three experiments examined the hypothesis that social isolation of weanling rats potentiates hedonic processes by examining the consumption of sucrose solutions. In the first experiment no differences in consumption were found between socially reared rats and isolation-reared rats allowed to consume sucrose in a familiar test apparatus. In a second experiment socially-reared rats and isolation-reared rats were food and water deprived. Again, no differences in consumption were found. In a third experiment socially reared and isolation-reared rats were allowed to consume sucrose presented in either an ascending or descending order of concentration. When given sucrose in an ascending order of presentation isolation-reared rats consumed significantly more sucrose than socially reared rats. This suggests that isolation-rearing increased the effects of positive contrast, and is consistent with other observations of increased incentive motivation in isolates.

Animals↗

The effects of isolation-rearing on preference by rats for a novel environment.

In the previous paper isolation-reared rats exhibited enhanced environmental neophobia under some conditions in an open-field. However, previous work has shown that isolation-reared rats have greater preferences for a novel environment in a dimly lit enclosed box. The hypothesis examined in the present experiments was that manipulation of the intrinsic aversive qualities of such an environment, by altering lighting conditions, could reverse the preference which isolation-reared rats exhibit for a novel chamber. When preference for a novel chamber was examined in a non-aversive environment in Experiment 1, isolation-reared rats exhibited a preference for a novel environment which was enhanced compared to social controls. When tested under more aversive white light conditions in Experiment 2, no differences in novelty preference were observed between isolation-reared and socially reared rats. Thus, the increased sensitivity to novel environments by isolation-reared rats appears to be critically dependent on the arousing or aversive properties of the testing conditions.

Animals↗

Retarded acquisition and reduced expression of conditioned locomotor activity in adult rats following repeated early maternal separation: effects of prefeeding, d-amphetamine, dopamine antagonists and clonidine.

Adult hooded rats exposed to a repeated maternal separation procedure during the neonatal period showed a blunted expression of locomotor hyperactivity conditioned to the presentation of the daily food ration. We have demonstrated that the expression of food-conditioned anticipatory hyperactivity is sensitive to the response-enhancing effects of systemic d-amphetamine (0.5; 1.0 mg/kg) and to the response-attenuating effects of the selective dopamine D2 antagonist sulpiride (8; 20 mg/kg), the selective dopamine D1 antagonist SCH 23390 (0.01; 0.022 mg/kg) and the mixed alpha 1/alpha 2 adrenoceptor agonist clonidine (5; 15 micrograms/kg) in a dose dependent manner. Animals from the early separation groups showed a reduced enhancement of activity in response to 0.5 mg/kg d-amphetamine and a greater attenuation of activity in response to 8 mg/kg sulpiride and 5 micrograms/kg clonidine. Female separated rats also exhibited an attenuated locomotor response to the unconditioned stimulant effects of 0.5 mg/kg systemic d-amphetamine. The experiments confirm that early maternal separation attenuates the response to conditioned appetitive cues in adult rats and implicate altered dopaminergic and noradrenergic function in the changes. It is possible that early maternal separation in the rat may offer a useful preparation for investigation of the neural substrates mediating affective development and affective psychopathology.

Adrenergic alpha-Agonists↗

Measurement issues in curve-shift analysis of apomorphine effects on rewarding brain stimulation.

The direct dopamine agonist apomorphine has been reported to reduce the rewarding efficacy of lateral hypothalamic (LH) self-stimulation. This effect has been claimed to support the notion that dopamine mediates the rewarding effects of LH self-stimulation. Using a standard rate-frequency curve-shift paradigm with ascending order of frequency presentation, we also found that apomorphine (0.1-0.8 mg/kg, SC) appeared to decrease LH self-stimulation reward. These apparent rightward curve shifts were exacerbated by shortening the test duration, which also produced a number of sessions in which the subjects did not respond at all. When the presentation order of stimulation frequencies was reversed, apomorphine did not produce large reward decreases. These results suggest that the previously reported effects of apomorphine on LH self-stimulation were the result of artifact, perhaps related to apomorphine-induced stereotypical behavior combined with rapid pharmacological recovery.

Animals↗

Social isolation in the rat produces developmentally specific deficits in prepulse inhibition of the acoustic startle response without disrupting latent inhibition.

A series of experiments examined the effects of 8 weeks of social isolation on spontaneous locomotor activity, prepulse inhibition (PPI) of the acoustic startle response, latent inhibition (LI) in a conditioned suppression paradigm, and basal and d-amphetamine stimulated dopamine (DA) release in the ventral striatum, as measured by in vivo microdialysis. Both isolation-reared animals (those isolated from the weaning age) and isolation-housed animals (those isolated as adults) were hyperactive when placed in a novel environment. Social isolation also led to deficits in PPI of the acoustic startle response that were specific to isolation-reared animals. Isolation rearing was without effect on the expression of LI but did lead to an enhanced response to systemic d-amphetamine in terms of striatal DA release. The data are discussed with respect to the involvement of ventral striatal DA mechanisms in the expression of PPI and LI, differences in the impact of social isolation in young and adult animals, and the utility of social isolation model as a nonlesion, nonpharmacologic means of perturbing ventral striatal DA function.

Acoustic Stimulation↗

Enhancement of amphetamine-induced locomotor activity and dopamine release in nucleus accumbens following excitotoxic lesions of the hippocampus.

This study tested the hypothesis that the hippocampus modulates dopamine-dependent function of the nucleus accumbens using behavioural and neurochemical evidence. Rats with bilateral lesions of the hippocampus induced by colchicine and kainic acid exhibited equivalent levels of spontaneous locomotor activity but a potentiation of the hyperactivity produced, dose-dependently, by D-amphetamine measured in photo-cell activity cages. The same rats subsequently received unilateral implantations of a microdialysis probe aimed at the nucleus accumbens and showed elevated levels of extracellular dopamine in response to D-amphetamine but no significant difference in basal values in comparison with sham-operated controls. The results are discussed in terms of functional interactions between the hippocampus and nucleus accumbens involving the control of mesolimbic dopamine release.

3,4-Dihydroxyphenylacetic Acid↗

The effects of excitotoxin lesions of the lateral hypothalamus on self-stimulation reward.

Unilateral microinjection into rat lateral hypothalamus (LH) of the excitotoxins ibotenic acid (IBO) and N-methyl-D-aspartic acid (NMDA) produced a local zone of neuronal death but also produced a zone of demyelination. The size of this demyelination zone was related to excitotoxin dose and was smaller than the zone of neuron killing. In behavioral testing, MFB self-stimulation reward and performance were measured with a rate-frequency curve-shift method before and after IBO or NMDA lesions of the LH. Excitotoxin lesions were made anterior or posterior to the LH electrode so that the zone of neuronal death, but not demyelination, extended to the electrode tip. These lesions produced small, temporary LH stimulation reward deficits, leading to the conclusion that intrinsic LH neurons are not a major substrate of MFB stimulation reward.

Animals↗

Acute and chronic desipramine treatment effects on rewarding electrical stimulation of the lateral hypothalamus.

Two weeks of chronic desipramine HCl (DMI) (10 mg/kg, IP) treatment did not alter reward or motor/performance components of intracranial self-stimulation (ICSS) as assessed with the rate-frequency method. Acute DMI treatment produced an ICSS reward decrement relative to saline control treatment, which was similar in size on Day 1 and Day 15 of chronic testing. The failure to find a chronic DMI effect on ICSS reward suggests that ICSS in normal rats may not be a valid animal model of depression. A better paradigm may be to test the ability of antidepressants to reverse a chronic reduction in ICSS reward function that is first produced by some other method.

Animals↗

Enhanced corticosterone release after a modified forced swim test in Fawn hooded rats is independent of rearing experience.

Recent findings have demonstrated that Fawn hooded (FH/Har) rats exhibit enhanced plasma corticosterone (CORT) responses compared to Wistar rats after exposure to an open field, whereas this effect was not influenced by early social experience. In contrast, it was found that behavior in a modified version of the Porsolt Forced Swim Test (Porsolt FST) was affected by both strain and social experience. An important part of this study included modifications of the Porsolt FST that allowed separation of multiple behavioral endpoints. The present experiment was conducted to determine if FH/Har rats also exhibit enhanced CORT responses after exposure to the modified forced swim test, and whether CORT levels might predict the behavioral response in this context. After the initial exposure in the modified forced swim test FH/Har rats had higher CORT levels than Wistar rats, but this difference was not affected by isolation rearing. However, CORT levels were not correlated with the main behavioral measures assayed in this test. Nonetheless, the data confirm that FH/Har rats have altered HPA axis responses to stressors.

Animals↗

Locomotor-stimulating effects of indirect dopamine agonists are attenuated in Fawn hooded rats independent of postweaning social experience.

The effects of the indirect dopamine (DA) agonists cocaine and D-amphetamine on locomotor activity were examined in Fawn hooded (FH) rats and Wistar rats. The effect of isolation rearing was also examined to determine if it might have different effects in these two strains. Contrary to previous findings in other rat strains, only small increases in locomotor-stimulating responses to low doses of cocaine were observed in the present study as a result of isolation rearing. However, at higher cocaine doses, locomotor activity was substantially attenuated in FH rats relative to Wistar rats. A similar pattern of effects was observed for amphetamine in FH rats but only at the intermediate dose. The effects of strain and rearing were independent. There was no evidence for interactions between these factors.

Animals↗