Elizabeth M. Somerville

Little and often: ingestive behavior patterns following hippocampal lesions in rats.

Lesions of both dorsal and ventral hippocampus were produced by multiple infusions of the excitotoxin AMPA. Meal patterns recorded before and after lesioning showed no change in total food intake, but a striking behavioral syndrome in which the lesioned rats took smaller meals 2-3 times as frequently and showed a similar change in drinking. In addition, lesioned rats alternated more frequently between feeding and drinking during a single bout of ingestive behavior. There were no group differences in the satiety sequence that followed a meal. In an open field test, lesioned rats showed enhanced locomotion in the periphery and reduced rearing. An olfactory habituation-dishabituation task showed that the lesioned rats investigated olfactory stimuli less but dishabituation to a changed stimulus was normal. The data are discussed in terms of changes in behavioral switching or a possible interoceptive agnosia following hippocampal damage.

5‐HT2C receptor activation inhibits appetitive and consummatory components of feeding and increases brain c‐fos immunoreactivity in mice

5‐Hydroxytryptamine (5‐HT)2C and 5‐HT1B receptors are implicated in the inhibitory modulation of feeding behaviour. However, their respective, and possibly different, roles have not been clearly identified because of a lack of selective 5‐HT2C receptor agonists. Here, using the putative, selective 5‐HT2C receptor agonist VER23779, we show that its effects on feeding are fully reversed by pretreatment with a selective 5‐HT2C receptor antagonist, but unaffected by pretreatment with either a 5‐HT1B or a 5‐HT2A receptor antagonist. In mice eating a palatable mash, feeding ends earlier, inactivity is increased but the behavioural satiety sequence is preserved. In a second‐order schedule of reinforcement with an initial, non‐food‐reinforced appetitive phase, VER23779 produces a much greater relative reduction in appetitive responding than the 5‐HT1B receptor agonist CP‐94,253. Increased c‐fos immunoreactivity patterns following VER23779 also differ from those described for CP‐94,253, in particular showing strong activation of the basolateral amygdala. The different behavioural consequences of 5‐HT2C and 5‐HT1B receptor activation may relate to the patterns of c‐fos immunoreactivity. In particular, the basolateral amygdala may have a role in maintaining response in the appetitive phase of the second‐order schedule and also be susceptible to serotonergic modulation through activation of 5‐HT2C receptors.

5-HT1B receptor knockout mice show a compensatory reduction in 5-HT2C receptor function.

Although null mutant (‘knockout’) mice have provided valuable animal models to complement traditional approaches to psychopharmacology, such animals may also show complex adaptations to the induced mutation. Here we demonstrate that serotonin1B (5‐HT1B) receptor knockout (KO) mice show adaptations in serotonin2C (5‐HT2C) receptor‐mediated functions. They show smaller reductions in food intake and locomotor activity in response to administration of 5‐HT2C receptor agonists that are not accounted for by altered drug disposition. These effects are not mimicked by pretreatment of wildtype (WT) mice with a 5‐HT1B receptor antagonist showing that they result from a longer term adaptation to the loss of 5‐HT1B receptor function and not from a short‐term interaction between 5‐HT1B‐ and 5‐HT2C‐mediated functions. In addition, we show that 5‐HT1B receptor KO mice have a lowered hypothalamic c‐fos response to the administration of 5‐HT2C receptor agonists. These results demonstrate that compensatory adaptations to the constitutive loss of 5‐HT1B receptors may be an important determinant of the altered response of 5‐HT1B KO mice to a variety of pharmacological challenges.

Tonic regulation of satiety by 5-HT1B receptors in the mouse: converging evidence from behavioural and c-fos immunoreactivity studies

Activation of 5‐HT1B receptors is thought to play an important role in the inhibitory influence of serotonin on feeding behaviour and body weight in mammals. Earlier studies have shown that 5‐HT1B‐knockout (KO) mice eat more and are heavier than wild‐type (WT) controls and that the selective 5‐HT1B receptor agonist CP‐94,253 reduces food intake in food‐deprived mice. Here we characterize the behavioural effects of both CP‐94,253 and the selective 5‐HT1B receptor antagonist SB224289 on feeding and other behaviours within the behavioural satiety sequence, and also report a c‐fos mapping study using CP‐94,253. CP‐94,253 produced a dose‐dependent suppression of food intake with a profile consistent with a selective effect on feeding behaviour. These effects were absent or reduced in 5‐HT1B‐KO mice and in WT mice pretreated with SB224289. SB224289 administered alone enhanced food intake consistent with impaired satiation; a similar effect was apparent in 5‐HT1B‐KO mice compared to WT. CP‐94,253 induced c‐fos in a range of structures previously implicated in the expression of feeding behaviour. These results suggest that the activation of 5‐HT1B receptors is an important component of endogenous satiation mechanisms in the mouse.

‘Asking pompeii questions’: a co-operative approach to Writing in the disciplines

This article is an account of a cooperative project to develop student writing within an interdisciplinary human sciences degree, in line with the ‘Writing in the Disciplines’ approach adopted in the USA that aims to develop student writing within mainstream teaching. The course tutor worked with a writing tutor to introduce a ‘writing strand’ into a first year course in archaeology. The project is described and evaluated with examples from students’ writing. On both subjective and objective measures the project was a success: students became more positive about their writing and their end of course essays generally improved. The article focuses particularly on the use of the technique of ‘freewriting’ as a way of strengthening students’ sense of their own voice and authority in their university writing.

The rat's not for turning : Dissociating the psychological components of cognitive inflexibility

Highlights • Non-rewarded or irrelevant prior associations are important for flexible responding.• Associations of reward and non-reward in reversal learning are neurally dissociable.• Disruption of prior irrelevant or rewarded associations cause pathological deficits.• Experimental paradigms of cognitive flexibility can be improved to aid translation.

Disturbance of meal patterning following nucleus accumbens lesions in the rat

In this study, we examined the effects of electrolytic lesions of the nucleus accumbens which had no obvious effect on body weight, or on the short term intake of solid food, sucrose and salt solutions. However in 24 h records of feeding and drinking lesioned animals took many more meals of shorter duration. Challenge with the dopamine D2 antagonist YM-09151-2 resulted in a decrease in feeding rate, together with a facilitation of meal size in drinking, in both control and lesioned subjects.

Dissociable Effects of 5-HT2C Receptor Antagonism and Genetic Inactivation on Perseverance and Learned Non-Reward in an Egocentric Spatial Reversal Task

Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg) in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS−), in a T- or Y-maze configuration. This was followed by three conditions; (1) Full reversal, where contingencies reversed; (2) Perseverance, where the previous CS+ became CS− and the previous CS− was replaced by a novel CS+; (3) Learned non-reward, where the previous CS− became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss on the development and maintenance of cognitive function.

Intra-accumbens baclofen, but not muscimol, mimics the effects of food withdrawal on feeding behaviour

Intra-accumbens stimulation of GABA receptors results in a robust increase in food intake. However the differential consequences of stimulating GABA(A) and GABA(B) receptors in the nucleus accumbens have not been extensively explored with respect to feeding behaviour. Here we compare the effects of the GABA(B) receptor agonist baclofen and GABA(A) receptor agonist muscimol, infused into the nucleus accumbens shell, on food intake and related behavior patterns. Baclofen (110-440 ρmol) dose dependently enhanced intake and delayed the onset of satiety within the test period as did the effects of 4-8h food withdrawal. Muscimol (220-660 ρmol) enhanced intake but also disrupted the sequence of associated behaviours at every dose tested. We conclude that GABA(B) receptors in the nucleus accumbens shell may play a role in relation to feeding motivation whereas GABA(A) receptors may, as previously suggested, have a more restricted role in relation to the motor components of approach to food and ingestion.

Intra-Accumbens Baclofen, But Not Muscimol, Increases Second Order Instrumental Responding for Food Reward in Rats

Stimulation of either GABAA or GABAB receptors within the nucleus accumbens shell strongly enhances food intake in rats. However the effects of subtype-selective stimulation of GABA receptors on instrumental responses for food reward are less well characterized. Here we contrast the effects of the GABAA receptor agonist muscimol and GABAB receptor agonist baclofen on instrumental responding for food using a second order reinforcement schedule. Bilateral intra-accumbens administration of baclofen (220–440 pmol) stimulated responding but a higher dose (660 pmol) induced stereotyped oral behaviour that interfered with responding. Baclofen (220–660 pmol) also stimulated intake of freely available chow. Muscimol (220–660 pmol) was without effect on responding for food on this schedule but did stimulate intake of freely available chow. Unilateral administration of either baclofen or muscimol (220 pmol) induced similar patterns of c-fos immunoreactivity in several hypothalamic sites but differed in its induction in the central nucleus of the amygdala. We conclude that stimulation of GABAA or GABAB receptors in the nucleus accumbens shell of rats produces clearly distinguishable effects on operant responding for food.