Amphetamine modifies ethanol intake of psychosocially stressed male rats

Studies of socially housed rodents have provided significant information regarding the consequences of exposure to stressors. Psychosocial stressors are known to alter the ingestion of ethanol and the activity of the dopaminergic neuronal system. Since both stressors and ethanol are known to affect the function of dopaminergic neurons, we employed amphetamine to assess the role of this neural system on the ingestion of ethanol by psychosocially stressed male rats. Male rats housed two per cage were designated as dominant or subdominant rats based on evaluations of agonistic behavior and body weight changes. The dyad-housed rats and a group of single-housed rats were sequentially assessed for ethanol intake after injections of saline or amphetamine (0.3, 0.9 or 2.7 mg/kg i.p.) both prior to dyad housing and subsequently again during dyad-housing. Prior to dyad housing ethanol intake of future subdominant rats was higher than that of future dominant rats. Dyad-housing significantly increased ethanol intake of dominant rats. Pre-dyad the highest dose of amphetamine potently depressed ethanol ingestion. Sensitivity to amphetamine's depressant effect on ethanol intake was higher at the dyad test in all subjects, most prominently in single-housed rats. In contrast to the single-housed rats, the dyad-housed rats displayed saccharin anhedonia. It can be concluded that dopaminergic system modulates, at least partially, the psychosocial stress-induced changes in ethanol intake. Furthermore, the level of ethanol ingestion at the pre-dyad test was predictive of future hierarchical status.     

The state-trait disjunction of anhedonia in schizophrenia: potential affective, cognitive and social-based mechanisms

Dysfunctions in affective experience reflect a pernicious feature of schizophrenia-spectrum pathology that are largely intractable under current treatment regimens. Of note, individuals with schizophrenia show robust and marked deficits in the experience of pleasure when assessed using “trait” measures of affect (i.e., trait questionnaires and clinical interview), but fail to demonstrate this anhedonia “in the moment” using controlled laboratory mood-induction procedures. The reasons for this disjunction are unclear, but the last decade has seen a number of recent studies tackling this issue. We conduct a comprehensive review of this literature here. Five different explanations for this state-trait disjunction are identified: 1) anticipatory hedonic experience deficit, 2) affective regulation deficit, 3) encoding-retrieval deficit, 4) representational deficit and 5) social-specific deficit theories. Our present article reviews each of these theories, placing them in context of the larger affective and cognitive neuroscience literatures when appropriate. Additionally, practical recommendations for future studies examining affective dysfunction within the schizophrenia-spectrum are discussed.     

Zinc supplementation provides behavioral resiliency in a rat model of traumatic brain injury

Depression, anxiety, and impairments in learning and memory are all associated with traumatic brain injury (TBI). Because of the strong link between zinc deficiency, depression, and anxiety, in both humans and rodent models, we hypothesized that dietary zinc supplementation prior to injury could provide behavioral resiliency to lessen the severity of these outcomes after TBI. Rats were fed a marginal zinc deficient (5 ppm), zinc adequate (30 ppm), or zinc supplemented (180 ppm) diet for 4 weeks followed by a moderately-severe TBI using the well-established model of controlled cortical impact (CCI). Following CCI, rats displayed depression-like behaviors as measured by the 2-bottle saccharin preference test for anhedonia. Injury also resulted in evidence of stress and impairments in Morris water maze (MWM) performance compared to sham-injured controls. While moderate zinc deficiency did not worsen outcomes following TBI, rats that were fed the zinc supplemented diet for 4 weeks showed significantly attenuated increases in adrenal weight (p < 0.05) as well as reduced depression-like behaviors (p < 0.001). Supplementation prior to injury improved resilience such that there was not only significant improvements in cognitive behavior compared to injured rats fed an adequate diet (p < 0.01), there were no significant differences between supplemented and sham-operated rats in MWM performance at any point in the 10-day trial. These data suggest a role for supplemental zinc in preventing cognitive and behavioral deficits associated with TBI.     

Increased susceptibility to development of anhedonia in rats with chronic peripheral nerve injury: Involvement of sleep deprivation?

The main purpose of the present study was to evaluate whether REM sleep deprivation (RSD) influences the development of anhedonia in rats in a peripheral neuropathy model induced by sciatic nerve constriction injury (CCI). Anhedonia was measured by assessing daily water/sucrose intake. Four groups were assessed: control (CTRL), CCI, RSD, and CCI + RSD (n = 8/group). Intake data were collected at baseline (mean of 3 days), on the 1st and 2nd days after a CCI or SHAM procedure, during 4 days of RSD, and during an additional 10 days (rebound period or equivalent in home-cage rats). Control rats spontaneously and progressively increased sucrose intake, reaching final daily volumes significantly greater than respective initial baseline amounts. RSD promoted an additional and immediate significant increase in sucrose intake during sleep deprivation days. The CCI group did not display a spontaneous, progressive increase in sucrose intake. When CCI was combined with RSD, the increase in sucrose intake induced by RSD was significantly lower than in animals submitted to RSD alone; the (CCI + RSD) group also failed to show a spontaneous and progressive increase in sucrose intake. The present findings indicate that animal model of chronic neuropathy exhibits reduced sucrose ingestion. Accordingly, this anhedonic condition that constitutes to the core manifestation of depressive states did not occur in response to a single episode of total RSD.     

Chronic mild stress induces widespread decreases in thyroid hormone alpha1 receptor mRNA levels in brain--reversal by imipramine

While considerable clinical evidence implicates thyroid hormones (THs) in depressive illness, the specific nature of this involvement remains unclear. The alpha1 subtype (TR-alpha1) is the most abundant TH receptor in brain. Here we investigated changes in TR-alpha1 mRNA in the chronic mild stress (CMS) model of depression. Rats were exposed to a CMS schedule for 3 weeks, which resulted in a progressive decreases in sucrose preference (an index of anhedonia). They were then treated daily with either imipramine (IMI, 10mg/kg) or vehicle (VEH) for 2 weeks before being sacrificed for quantitative in situ hybridization analyses of TR-alpha1 mRNA throughout the brain. Results indicated that CMS followed by VEH induced widespread decreases in TR-alpha1 mRNA in brain. In contrast, CMS-exposed rats receiving IMI for the last 2 weeks prior to sacrifice showed full recovery of sucrose preference. Furthermore, brain TR-alpha1 mRNA levels in these animals were similar to those of non-stressed controls receiving either SAL or IMI. These results reveal that TR-alpha1 mRNA brain levels are very sensitive to CMS effects. The reversal of both anhedonic and TR-alpha1 effects of CMS by IMI suggests that TR-alpha1 may play a role both in stress-induced depressive symptoms and in their reversal by antidepressant interventions.     

Role of estradiol withdrawal in ‘anhedonic’ sucrose consumption: A model of postpartum depression

Previously, a hormone-simulated pregnancy (HSP), and the subsequent ‘postpartum’ withdrawal in estradiol has been shown to precipitate depressive-like behaviours in the forced swim test in female rats. In this study, we used the HSP and ‘postpartum’ withdrawal to investigate the impact on sucrose consumption, a model of anhedonia. Rats were assigned to “postpartum”, “postpartum” + EB (estradiol benzoate), “postpartum” + IMI (imipramine; a tricyclic antidepressant), “postpartum” + DPN (diarylpropionitrile; an ERβ agonist), or ovariectomized (OVX) controls and OVX + IMI treatments. All “postpartum” groups received daily hormone injections (estradiol and progesterone) over 23 days to simulate pregnancy, while IMI groups also received daily injections of imipramine. After Day 23, “postpartum” rats were withdrawn from the hormone regimen (mimicking the postpartum decrease in gonadal hormones), and then received daily injections of compounds indicated (DPN, EB, IMI). Rats were tested for consumption of, and preference for, sucrose weekly at baseline, during ‘pregnancy’ and on ‘Postpartum’ Days 2-3. During the ‘postpartum’ period rats in the “postpartum” group had lower sucrose consumption and preference compared to during late-‘pregnancy’, but no decrease in ‘postpartum’ consumption or preference was seen in any other groups except “postpartum” + IMI and a decrease in sucrose preference only in the postpartum + EB group from mid-‘pregnancy’ to ‘postpartum’. The OVX  + IMI group had decreased sucrose consumption relative to OVX controls, suggesting a negative effect of imipramine on sucrose consumption. Together, these results suggest an important, though complex, role for gonadal hormones in the behavioral changes accompanying this model of depression.     

The emotional paradox: Dissociation between explicit and implicit processing of emotional prosody in schizophrenia

People with schizophrenia show well-replicated deficits on tasks of explicit recognition of emotional prosody. However it remains unclear whether they are still sensitive to the implicit cues of emotional prosody, particularly when they exhibit high levels of social anhedonia. A dual processing model suggesting a dissociation between the neural networks involved in explicit and implicit recognition of emotional prosody has yet to be validated.21 participants with schizophrenia and 21 controls were recruited. In the explicit recognition task, individuals listened to semantically neutral words pronounced with two different emotions and judged their emotional prosody. In the vocal emotional Stroop task, patients and controls listened to words with a positive or negative emotional valence pronounced with congruent or incongruent emotional prosody and judged their emotional content. Patients were also assessed with the Chapman Anhedonia Questionnaire and the Schizophrenic Communication Disorders scale.Individuals with schizophrenia were impaired in their explicit recognition of emotional prosody related to controls. In contrast, they showed a vocal emotional Stroop effect that was identical to controls for reaction time and greater for accuracy: patients were still sensitive to implicit emotional prosody. In addition the vocal emotional Stroop score increased with social anhedonia but was unrelated to communication disorders.Whereas explicit vocal affect recognition is impaired, implicit processing of emotional prosody seems to be preserved in schizophrenia. Our results provide evidence that at a behavioural level, the implicit and explicit processing of emotional prosody can be dissociated. Remediation of emotional prosody recognition in schizophrenia should target cognitive rather than sensory processes.     

The validity of Psychosis Proneness Scales as vulnerability indicators in recent-onset schizophrenia patients

The Psychosis Proneness Scales developed by the Chapmans and colleagues [Chapman, J.P., Chapman, L.J., Kwapil, T.R. Scales for the measurement of schizotypy. In: Raine., A., Lencz, T., Mednick, S.A., (Eds.). Schizotypal Personality. New York: Cambridge University Press, 1995. pp. 79–109] are widely used to identify non-patient individuals who are hypothesized to possess heightened vulnerability to schizophrenia and related psychopathology. Yet surprisingly little is known about whether schizophrenia patients themselves show abnormalities on these scales across different clinical states, as would be expected for vulnerability indicators. Scores on four of the Psychosis Proneness Scales were evaluated at three assessment points over a 15-month period in healthy controls (n = 54) and in recent-onset schizophrenia patients (n = 72) who experienced symptom fluctuations across assessments. Patients showed steady elevations on the Physical Anhedonia Scale across time and clinical state, consistent with a stable vulnerability indicator. Patients had higher scores on the Perceptual Aberration and Magical Ideation Scales than controls throughout the follow-up period but scores also changed across clinical states, consistent with a mediating vulnerability indicator. Patients had higher scores on the Impulsive Non-Conformity Scale than controls only during a psychotic state, reflecting an episode indicator. The longitudinal characteristics of these scales in people who are actually diagnosed with schizophrenia provide key evidence for the validity of three commonly used psychometric indicators of vulnerability to psychosis.     

Computerized measurement of negative symptoms in schizophrenia

Accurate measurement of negative symptoms is crucial for understanding and treating schizophrenia. However, current measurement strategies are reliant on subjective symptom rating scales, which often have psychometric and practical limitations. Computerized analysis of patients' speech offers a sophisticated and objective means of evaluating negative symptoms. The present study examined the feasibility and validity of using widely-available acoustic and lexical-analytic software to measure flat affect, alogia and anhedonia (via positive emotion). These measures were examined in their relationships to clinically-rated negative symptoms and social functioning. Natural speech samples were collected and analyzed for 14 patients with clinically-rated flat affect, 46 patients without flat affect and 19 healthy controls. The computer-based inflection and speech rate measures significantly discriminated patients with flat affect from controls, and the computer-based measure of alogia and negative emotion significantly discriminated the flat and nonflat patients. Both the computer and clinical measures of positive emotion/anhedonia corresponded to functioning impairments. The computerized method of assessing negative symptoms offered a number of advantages over the symptom scale-based approach.     

Chronic mild stress generates clear depressive but ambiguous anxiety-like behaviour in rats

A 3-week chronic mild stress (CMS) protocol decreased sucrose preference of rats and increased immobility in the forced swim test. It also induced social avoidance and increased grooming, but acted as if reducing anxiety in the plus-maze. Sucrose preference and social avoidance, but not other measures of the behaviour, showed significant correlation. We conclude that CMS-induced depression-like behaviour is associated with social avoidance, a seemingly anxiety-related measure, but not with other anxiety-like traits in rats.