Ana Maria Basso

Effects of selective dopamine D1 or D2 receptor blockade within nucleus accumbens subregions on ingestive behavior and associated motor activity

Two anatomically and neurochemically distinguishable regions of the nucleus accumbens (Acb), the core and the shell, have been shown to differentially regulate feeding behavior. Nevertheless, despite the well-known role of Acb dopamine in the modulation of motivated behaviors, there have been no studies directly comparing the effects of acute dopamine receptor blockade in the Acb core versus the Acb shell on feeding. In this study, D1- or D2-selective dopamine receptor antagonists were infused bilaterally into the Acb core or shell of hungry rats, whereupon feeding, drinking, and spontaneous motor activity were monitored. Both the D1 antagonist SCH 23390 (0, 1, and 2 microg/0.5 microl) and the D2 antagonist raclopride (0, 1, and 2 microg/0.5 microl) markedly suppressed ambulation and rearing when infused into either the Acb core or shell. Total food intake and latency to begin feeding were unaffected by either drug in either site. SCH 23390 in the Acb shell, and raclopride in the Acb core or shell, significantly decreased the total number of feeding bouts. In the Acb core, raclopride produced a small but statistically significant increase in overall feeding duration. Dopamine receptor blockade in either site tended to increase mean feeding bout duration. Measures of drinking behavior were generally unaffected. Hence, dopamine receptor blockade in either the Acb core or shell of hungry rats suppressed spontaneous motor activity and shifted the structure of feeding towards longer bout durations, but did not alter the total amount of food consumed. In the Acb shell, the effects of D1 receptor blockade tended to be of greater magnitude than the effects of D2 receptor blockade, although major differences between core and shell effects were not observed. These results are discussed with regard to current theories of dopaminergic control of feeding behavior, and with reference to the functional heterogeneity of Acb subregions.

Feeding induced by GABAA receptor stimulation within the nucleus accumbens shell : Regional mapping and characterization of macronutrient and taste preference

This study investigated the areas of the nucleus accumbens shell involved in the modulation of feeding behavior by GABAergic stimulation and characterized this response using macronutrient diets as well as saline, sucrose, and saccharin solutions. The GABA agonist muscimol induced a pronounced feeding response when infused in the medial nucleus accumbens shell but not in the ventral or lateral accumbens shell. In the macronutrient preference study, muscimol increased the intake of both high fat and high carbohydrate diets when presented separately. When both diets were available simultaneously, muscimol stimulated feeding of both diets to the same degree. Muscimol elicited a robust increase in the consumption of sucrose solution. However, no effect of muscimol was demonstrated for water, saline, or saccharin intake. These findings provide evidence for a selective role for GABA-sensitive neurons in the medial accumbens shell in the regulation of ingestive behavior and further suggest that GABA(A) receptors in this region do not modulate palatability, macronutrient selection, or rewarding properties of food.

Time-dependent induction of anxiogenic-like effects after central infusion of urocortin or corticotropin-releasing factor in the rat

Abstract.Rationale: Corticotropin-releasing factor (CRF) and urocortin (Ucn) belong to the CRF-related family, share a high degree of structural homology and bind to CRF receptors. However, compared with CRF, Ucn was shown to display either weaker or similar anxiogenic-like effects in vivo. Objective: To compare the anxiogenic-like responses of rats injected intracerebroventricularly (ICV) with different doses of either rat/human CRF (r/hCRF) or rat Ucn (rUcn) at different intervals after injection. Methods: Rats were tested on three validated paradigms of emotional behavior [i.e. elevated plus-maze (EPM), defensive withdrawal (DW) and conflict test (CT)] 5 and 30xa0min after treatment. Results: In the EPM test only r/hCRF, but not rUcn, produced anxiogenic-like effects at the dose of 1.0xa0µg, when the peptides were injected 5xa0min before testing. At 30xa0min after injection, both peptides caused a significant reduction of open arms exploration, rUcn being effective at 0.01xa0µg. In the DW test both peptides were equally potent in decreasing the exploratory behavior and increasing the time spent in the chamber at the dose of 1.0xa0µg when tested 30xa0min after injection. In the CT both rUcn (0.25–1.0xa0µg) and r/hCRF (0.75–1.0xa0µg) decreased significantly the responding in the punished component. However, rUcn reduced food responding also in the unpunished component possibly due to its powerful anorectic activity. Conclusions: Comparison of anxiogenic-like activities of r/hCRF and rUcn at doses up to 1.0xa0µg revealed striking differential effects that depended on the time of testing after ICV peptide injection, and on the paradigm of anxiety used. These results suggest that the onset of r/hCRF and rUcn actions related to behavioral responses to anxiety is likely to depend on brain peptide-specific mechanisms including binding properties to CRF-receptors, differential distribution to specific functional brain sites and the distribution and effectiveness of binding-protein interactions.

Effect of chronic variable stress on monoamine receptors: influence of imipramine administration

Adult male rats were exposed to a series of unpredictable stressors, a paradigm considered to be a model of experimental depression, with or without concurrent administration of imipramine. One day after the last stress event of the chronic regime, binding of cortical beta-adrenoreceptors and the behavioral serotonin (5-HT) syndrome induced by 5-methoxy-N,N,dimethyltryptamine (5-MeODMT) were determined in all the experimental groups. Stressed rats showed an up-regulation of cortical beta-adrenergic sites, while similar values to control rats were observed when stressed animals were administered imipramine. Regarding the behavioral 5-HT syndrome, comparable behavioral scores were observed between controls and chronically stressed rats. The combination of chronic exposure to different stressors with imipramine treatment resulted in a significant increase of forepaw treading and Straub tail scores. The probable facilitation of behavioral deficits induced by this scheme of chronic stress and the recovery following concurrent administration of imipramine are discussed.

A dopaminergic mechanism is involved in the ‘anxiogenic-like’ response induced by chronic amphetamine treatment: a behavioral and neurochemical study

The purpose of this study was to examine the influence of chronic d-amphetamine (AMPH) treatment (2 mg/kg i.p., for 9 consecutive days) on behavioral and neurochemical responses to a subsequent exposure - 4 days after the last AMPH injection--to the elevated plus-maze (EPM), as well as to determine the involvement of a dopaminergic mechanism in that influence. Results showed that chronic AMPH treatment induced an anxiogenic-like response when animals were evaluated in the EPM test. Pretreatment with either haloperidol (HAL, 1 mg/kg i.p., 20 min prior to each injection) or SCH-23390 (0.1 mg/kg i.p., 10 min prior to each injection) completely abolished the chronic AMPH-induced anxiogenic-like effect displayed in the EPM test. However, sulpiride pretreatment (60 mg/kg i.p., 10 min prior to each AMPH injection) did not modify such effect. In addition, rats treated with AMPH and subsequently exposed to the EPM, showed a decrease in the maximal GABA-stimulated chloride uptake in cortical microsacs. HAL pretreatment restored the maximal chloride uptake induced by chronic AMPH. Altogether, these results suggest that: (1) previous exposure to chronic AMPH treatment induces an increased emotional response following a conflict situation, (2) dopamine D(1) receptors are mainly involved in chronic AMPH-induced changes in the behavior displayed in EPM test, and (3) an interaction between GABAergic and dopaminergic mechanisms may be implicated in neurochemical and behavioral changes induced by chronic AMPH treatment.

Seven-day variable-stress regime alters cortical β-adrenoceptor binding and immunologic responses: Reversal by imipramine

Rats were submitted daily to a variable stressor for 1 week with or without concurrent imipramine (IMI) administration. One day after the last injection or stressful event, binding of cortical beta-adrenoceptors was determined in all experimental groups. Another group of chronically stressed animals with or without concurrent IMI administration were sacrificed 24 h following the last stress or injection treatment, and several immunologic parameters were evaluated. Chronically stressed rats showed an enhanced number of cortical beta-adrenergic sites without changes in their affinity. This effect was not present following concurrent administration with the antidepressant. In addition, a decreased percentage of T lymphocytes and a reduced delayed-type hypersensitivity reaction was also observed in stressed animals. Both responses were no longer evident when stressed rats were previously administered IMI. A possible link between behavioral, neurochemical, and immunologic alterations due to the stress regime is discussed.

Chronic variable stress facilitates tumoral growth : reversal by imipramine administration

The present study was conducted to examine whether a chronic variable stress procedure (CVS)--an animal model of depression--facilitates tumor growth, and whether this effect can be modified by concurrent administration of the antidepressant imipramine (IMI). Unstressed rats, with or without previous administration of the immunosuppressive agent cyclosporine (CS), were inoculated with 5 x 10(6) cells of a sarcoma. Another group of rats was inoculated with tumoral cells and later exposed to the CVS procedure with or without concurrent administration of IMI (10 mg/kg, i.p.). An additional group of animals was treated with CS and later given daily injections of IMI (10 mg/kg, i.p.) without stress manipulation. A lack of tumoral development was observed in unstressed animals without previous injections of CS, whereas, prior injections of this immunosuppressive agent increased tumoral growth in unstressed animals. Exposure to the CVS procedure facilitated tumoral growth even in animals without CS injections. This effect was clearly attenuated when chronically stressed rats were concurrently given IMI. These findings support the notion that the development of a tumoral process is facilitated when a state of experimental depression is induced and that the reversal of such a state by antidepressant treatment results in the inhibition of tumor development.

Chronic Amphetamine Facilitates Immunosuppression in Response to a Novel Aversive Stimulus: Reversal by Haloperidol Pretreatment

The effect of chronic d-amphetamine sulfate (AMPH) treatment (nine daily injections, 2 mg/kg i.p.) on subsequent foot shock stress-induced immunological response was investigated. In addition, the potential role of a dopaminergic (DA) mechanism in the development of chronic AMPH-induced changes in stress-influenced immune responses was characterized. Exposure to foot shock stress decreased the percentage of T-lymphocytes, and reduced the delayed-type hypersensitivity reaction (DTH) in chronically AMPH-pretreated rats relative to vehicle-treated controls. Both of those stress-induced immunosuppressive responses were no longer evident when AMPH-pretreated rats were injected with haloperidol (HAL, 1 mg/kg i.p.) 30 min prior to each daily AMPH injection. The present findings are indicative of a modulatory role for dopamine in the facilitating process induced by AMPH on stress-induced immunosuppressive effects.

Perinatal undernutrition reduced ethanol intake preference in adult recovered rats

Adult female rats submitted to a protein deprivation schedule at perinatal age (from 14th day of fetal life until 50 days of age) were tested for alcohol intake in a preference test. When compared with control animals, experimental rats exhibited higher overall fluid intake. Nevertheless, in terms of ethanol preference these subjects evidenced lower preference to this drug. A test for assessing ethanol olfactory preference did not show any differences between control and experimental rats in basal conditions. However, after repeated exposure to alcohol, deprived rats showed an aversion to ethanol odor, while controls evidenced the opposite effect, i.e., heightened preference. Possible differences to the aversive effects of ethanol between control and experimental animals were assayed by means of two taste aversion tests, by associating alcohol to sucrose or NaCl. No differences were detected between both groups of rats. These results demonstrate that early undernutrition reduces ethanol preference in a free choice situation. Such an effect could be due, at least partially, to odor aversion developed by repeated exposure.

Chronic restraint attenuates the immunosuppressive response induced by novel aversive stimuli

The exposure to a novel aversive event, such as foot shock, induced a decrease in the percentage of T lymphocytes and a clear reduction in the delayed-type hypersensitivity reaction (DTH). This immunosuppressive response to an acute stressor was absent in rats that were previously exposed to a chronic immobilization stress regime (2 h daily during 7 consecutive days), but was still present in animals with prior exposure to only one or three restraint sessions. No stress effect was observed in other immunologic parameters, such as the percentage of B lymphocytes or the hemagglutinin titer, in any of the experimental treatments. The possible involvement of central adaptive mechanisms in the attenuation of the immunosuppressive response induced by an acute stress is discussed.