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B J Everitt

Publications and source records attributed to B J Everitt.

At least 181 records · Page 10Linked to original sources

Increased weight gain and reduced activity in brown adipose tissue produced by depletion of hypothalamic noradrenaline.

The effects of hypothalamic noradrenaline depletion produced by injection of 6-hydroxydopamine (6-OHDA) into the vicinity of cell bodies of the ventral noradrenergic bundle (VNAB) on weight gain, food intake and brown adipose tissue (BAT) activity (as measured by GDP binding in BAT mitochondria), were examined in rats at two different ages and under two different dietary conditions (chow and chow plus palatable cheese). VNAB lesions enhanced weight gain in the chow plus cheese diet conditions and produced small increases in feeding. These effects were parallelled by reductions in BAT activity in the VNAB group, suggesting a reduced capacity for dietary thermogenesis which may contribute to the significant overweight.

Adipose Tissue, Brown↗

Immunohistochemical evidence for a new group of catecholamine-containing neurons in the basal forebrain of the monkey.

Using a specific antibody to the catecholamine (CA) synthesizing enzyme, tyrosine hydroxylase (TH), in combination with the avidin-biotin-peroxidase complex method, we have found evidence for the existence of a new CA-containing cell group extending from the orbitofrontal cortex through the olfactory and pyriform cortices in the brain of two species of monkey. The TH-positive perikarya, which are 4000-5000 in number, are situated within the outer layers of these cortices and also within the olfactory tubercle and horizontal limbs of the diagonal band of Broca. They have small (10-20 microns) somata of round or oval shape. A majority are bipolar with long, slender dendrites but some are small, multipolar with widely branching dendrites. The shape and laminar distribution of these TH-positive neurons suggest that they may serve functions as cortical interneurons.

Animals↗

Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal.

Five experiments examined the effects of destruction of the dorsal noradrenergic bundle (DNAB), arising in the locus coeruleus, both on brightness and spatial visual discrimination, and selective attention. An analogue o Leonard's 5-choice serial reaction task for human subjects was used. Hungry rats were trained to detect brief (0.5 sec) flashes of light presented randomly in one of 5 locations with a fixed intertrial interval of 5 sec, paced by the rat. Correct responses were rewarded with food and incorrect responses punished by time-out (darkness + delay). Following training to high levels of accuracy (80%, with less than 20% errors of omission), rats received either 6-OHDA (4 micrograms/2 microliters) injected bilaterally into the trajectory of the dorsal bundle, or injection of vehicle (0.1% ascorbic acid in 0.9% saline). The 6-OHDA lesion was sufficient to reduce cortical NA by 84%. Performance on both the spatial discrimination and brightness (produced by graded reductions in the brightness of the stimuli) discrimination was unaffected by DNAB lesions. However, the DNAB lesion produced significant decreases in accuracy and increases in omissions when the stimuli were presented at faster, unpredictable rates. In addition, although intense white noise failed to produce differential impairments when presented simultaneously with the visual discriminanda, the DNAB lesion significantly impaired accuracy when the noise was presented immediately prior to, but not overlapping, the onset of the visual stimuli. The implications of this pattern of deficits in performance found following DNAB lesions is discussed in terms of disruptive effects of cortical NA depletion upon mechanisms of selective attention and arousal.

Animals↗

Changes in body weight and food-related behaviour induced by destruction of the ventral or dorsal noradrenergic bundle in the rat.

Three experiments contrasted the effects of 6-hydroxydopamine-induced lesions of the ventral noradrenergic and dorsal noradrenergic projections, predominantly to hypothalamus and cortex, respectively, upon body weight changes and food-related behaviour in the rat. In general, ventral noradrenergic bundle lesions enhanced weight gain and these effects were exaggerated by the provision of palatable cheese to the standard chow diet. In contrast, lesions of the dorsal noradrenergic bundle produced minor changes in body weight. Associated with the effects of ventral noradrenergic bundle lesions were hyperphagia, enhanced suppression of intake of food adulterated with quinine, (at high concentration), a small attenuation of food neophobia, and enhanced acquisition, but not performance, of the eating response to tail-pinch stimulation. These ventral noradrenergic bundle lesions failed to alter basal activity levels, amphetamine anorexia or the diurnal pattern of eating or activity. In contrast, lesions of the dorsal noradrenergic bundle did not produce either hyperphagia or enhanced rejection of food adulterated with quinine. However, there was a strong attenuation of food neophobia and a retarded acquisition (but unimpaired performance) of eating in response to tail-pinch stimulation. The results are discussed in connection with previous studies of ventral and dorsal noradrenergic bundle lesions, with the effects of ventromedial hypothalamic lesions and with the underlying behavioural and physiological processes that mediate these contrasting effects of different neuroanatomical patterns of central noradrenaline depletion.

Animals↗

The effects of lesions to ascending noradrenergic neurons on discrimination learning and performance in the rat.

Three experiments examined the effect of central noradrenergic depletion on the acquisition and performance of a temporal discrimination in auditory or visual modalities. In Experiment 1, 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle significantly retarded acquisition compared to a similarly lesioned ventral noradrenergic bundle-group, two sham-operated and one unoperated control group. In Experiment 2, the acquisition impairment produced in the dorsal noradrenergic bundle group was replicated, for both auditory and visual modalities, by lesions depleting hippocampal and neocortical noradrenaline by over 80%. In rats subsequently switched to discriminations involving the unfamiliar modality, the dorsal-bundle lesion also impaired acquisition several weeks after surgery. Experiment 3 showed significantly impaired performance in rats with dorsal bundle lesions when training prior to surgery had not resulted in better than chance performance. In rats previously trained to criterion, the dorsal bundle lesion transiently, but non-significantly, impaired performance. In rats performing better than chance, but not having reached criterion, there were no significant effects of the dorsal bundle lesion. Subsequent manipulations of deprivation and difficulty of discrimination in general failed to distinguish between the dorsal bundle lesion and sham-groups, suggesting that the acquisition impairment did not result from simple sensory or motivational effects. Reducing the interstimulus interval did impair the dorsal bundle group more than controls. However, there was no evidence of altered "distractibility" in the lesioned group when the alternative modality was introduced as a distractor. The results are discussed in terms of other acquisition deficits shown by rats with central noradrenaline depletion and their significance for determining the functions of the projections from the locus caeruleus via the dorsal noradrenergic bundle to the neocortex and hippocampus.

Afferent Pathways↗

Effects of passive immunization against testosterone on the sexual activity of female rhesus monkeys.

Active immunization of an ovariectomized rhesus monkey against testosterone-3(0-carboxymethyl)oxime-bovine serum albumin produced an antiserum with a high degree of specificity towards testosterone. Passive immunization of ovariectomized, oestrogen-treated monkeys with this antiserum resulted in significant reductions in proceptive and/or receptive behaviours in the majority of animals. This effect could be reversed by treatment with 17 alpha-methyltestosterone, a steroid which showed only 6% cross-reaction with the antiserum. Passive immunization caused an increase in the binding of testosterone by the gamma-globulin fraction of serum isolated by treatment with 2-ethoxy-6,9-diaminoacridine lactate. The present findings emphasize the importance of androgens of adrenal origin in the regulation of sexual behaviour in the female rhesus monkey.

Animals↗

The organization of indoleamine neurons in the brain of the rhesus monkey (Macaca mulatta).

The organization of indoleamine-containing neurons throughout the CNS of Macaca mulatta was examined with Falck-Hillarp histofluorescence and radioenzymatic biochemical techniques. Indoleamine-containing cell bodies, corresponding to the serotonin-containing groups B1 to B9, were observed within the brain stem. The pontine cell populations, however, were far more numerous than in the rat and represented caudal subpopulations of cells within the nucleus raphe dorsalis (B7) and nucleus centralis superior (B8). Additionally, the pontine indoleamine-containing cells in M. mulatta extended laterally through the tegmentum such that they were often adjacent to catecholamine-containing neurons of the locus coeruleus complex. Ascending indoleamine-containing fiber bundles, similar to those defined in nonprimate mammals, were also observed within the pons and mesencephalon. Regional differences in the distribution of serotonin within hypothalamic nuclei and other forebrain regions of M. mulatta were revealed through a highly sensitive radioenzymatic assay in conjunction with microdissection. Significant concentrations of serotonin were evident in most areas, although the levels of this neurotransmitter were much lower in the median eminence region and nucleus suprachiasmaticus than in the rat. These differences may reflect variations in the control neuroendocrine events in the two species.

Afferent Pathways↗

The organisation of catecholamine-containing neurons in the brain of the rhesus monkey (Macaca mulatta).

The distribution of catecholamine neurons in the brains of several rhesus monkeys (Macaca mulatta) was studied by means of the Falck-Hillarp formaldehyde histofluorescence technique. Catecholamine-containing cell bodies in the medulla and pons were found to correspond essentially to the noradrenaline cell groups A1-A7, originally defined in the rat. The pontine catecholamine neurons of the locus coeruleus (A6) and subcoeruleal tegmental areas (A6, A5 and A7) are, however, far more numerous in M. mulatta; observations which agree with reports in other primate species and carnivores. Rostrally projecting fibres, analogous to the ascending 'ventral' and 'dorsal' noradrenaline bundles described in other species, have also been observed in addition to those equivalent to the dorsal periventricular system. The large number of cells present throughout the mesencephalon represent dopamine cell groups A8-A10, while small populations of catecholamine neurons within the periventricular regions of the hypothalamus correspond to groups A11-A14. A prominent terminal innervation of the diencephalon (hypothalamus) is also evident in M. mulatta. Although similar in general terms to that in other species, several important variations are apparent. These and other differences noted above may underlie species specific variations in behaviour.

Animals↗

Alterations in sexual behaviour and 5-hydroxyindoleacetic acid in the cerebrospinal fluid of female rhesus monkeys treated with clomipramine.

Clomipramine markedly decreases the proceptivity and receptivity of female rhesus monkeys paired with males in the laboratory. These behavioural changes are correlated with cerebrospinal fluid levels of 5-hydroxyindoleacetic acid and with noradrenaline and serotonin uptake, both in vivo and in vitro. Detailed studies of this kind should help to elucidate the effects of antidepressant therapy on sexual activity in man, and the wider relationship between cerebral amines and behaviour.

Animals↗

On the action of nicotine and cotinine on central 5-hydroxytryptamine neurons.

The actions of nicotine, and its main metabolite cotinine, on 5-hydroxytryptamine (5-HT) neurons in the brain of the rat have been assessed biochemically (on turnover, uptake, release, overflow and binding of 5-HT in brain) and functionally (on extensor reflex activity, which is 5-HT dependent). Nicotine and cotinine in repeated doses of 2 mg/kg caused a reduction of brain 5-HT turnover, which was not blocked by pretreatment with mecamylamine, and nicotine sifnificantly inhibited the effects of norfenfluramine and 5-methoxydimethyltryptamine on extensor reflex activity, effects counteracted by mecamylamine. In low concentrations cotinine weakly inhibits the uptake and retention of 5-HT and also increases its spontaneous release in vitro. The biochemical findings suggest that the reduction of 5-HT and also increases its spontaneous release in vitro. The biochemical findings suggest that the reduction of 5-HT turnover caused by high doses of nicotine are mediated, at least in part, by its main metabolite cotinine. The experiments on extensor reflexes indicate that nicotine can block the functional expression of 5-HT receptor activity in the spinal cord by an action beyond the 5-HT receptor at nicotine-like cholinergic receptors whose location is also discussed.

Amides↗