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The psychogenetically selected Roman high- and low-avoidance rat lines: a model to study the individual vulnerability to drug addiction
No full textNeonatal ventral hippocampal lesions potentiate amphetamine-induced increments in dopamine efflux in the core, but not the shell, of the nucleus accumbens
No full textBiol Psychiatry. 2006 Dec 1;60(11):1188-95. Epub 2006 Aug 24.
Neonatal ventral hippocampal lesions potentiate amphetamine-induced increments in
dopamine efflux in the core, but not the shell, of the nucleus accumbens.
Corda MG, Piras G, Giorgi O.
Department of Toxicology, University of Cagliari, Cagliari, Italy.
BACKGROUND: In rats, neonatal ventral hippocampal lesions (NVHLs) result in the
postpubertal emergence of alterations reminiscent of several features of
schizophrenia, including increased responsivity to the behavioral effects of
amphetamine (AMPH). The precise nature of presynaptic aspects of accumbal
dopamine (DA) function in these alterations is however uncertain: previous
studies have found that the exacerbated responses to AMPH of NVHL rats are
associated with either decreased or unchanged DA efflux in the nucleus accumbens
(NAc) as compared with shams. Because these studies investigated DA output in the
whole NAc, it was considered of interest to examine the impact of NVHLs on DA
transmission in NAc subregions involved in distinct aspects of goal-directed
behavior.
METHODS: The effects of AMPH (.25 mg/kg, subcutaneous) on the accumbal DA efflux
of adult rats were evaluated using brain microdialysis, and motor activity was
recorded alongside dialysate sample collection.
RESULTS: The enhanced behavioral responsivity to AMPH of NVHL rats is associated
with potentiation of AMPH-induced DA output in the NAc core and a concomitant
attenuation of DA overflow in the NAc shell.
CONCLUSIONS: The functional alterations in the NAc core induced by NVHLs provide
a link between the hippocampal damage and striatal DA hyperactivity in
schizophrenia.
PMID: 16934777 [PubMed - indexed for MEDLINE
Differential effects of voluntary ethanol consumption on dopamine output in the nucleus accumbens shell of Roman high- and low-Avoidance rats: A behavioral and brain microdialysis study
No full textThe Roman high- (RHA) and low-Avoidance (RLA) rats were selectively bred for rapid vs poor acquisition of two-way active avoidance behavior. These lines differ in numerous behavioral traits, with RLA rats being more fearful/anxious than RHA rats, and the latter being novelty-seekers and showing larger intake of, and preference for, addictive substances including ethanol (ETH). Moreover, several differences in central dopaminergic, serotonergic, and GABAergic functions have been reported in these two lines. Since those neural systems are involved in the regulation of ETH consumption, it was considered of interest to investigate: 1) the differences in ETH intake and preference between RHA and RLA rats, 2) the effects of ETH on DA release in the shell of the nucleus accumbens (AcbSh) using brain microdialysis. ETH solutions of increasing concentrations (2%- 10%) were presented on alternate days in a free choice with water. To examine ETH intake and preference stability, animals were subsequently switched to daily presentations of 10% ETH for 10 consecutive days. RHA rats consumed significantly larger amounts of ETH and displayed higher ETH preference than did RLA rats throughout the acquisition and maintenance phases. Following chronic exposure to ETH the animals were habituated to a restricted access to ETH schedule (2% ETH, 2 h per day × 4 days) before surgical implantation of a dialysis probe in the AcbSh. Under these experimental conditions, voluntary ETH intake (2%, 1 h, p.o.) produced a significant increase in accumbal DA output in RHA rats but not in their RLA counterparts. Finally, the i.p. administration of ETH (0.25 g/kg) to naïve Roman rats produced a significant increment in accumbal DA output only in RHA rats. These results indicate that the mesolimbic dopaminergic system of RHA rats is more responsive to the effects of ETH than that of RLA rats
Repeated morphine injections induce behavioural sensitization in Roman high-, but not in Roman low-avoidance rats
No full textThe selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats for, respectively, rapid vs poor active avoidance acquisition has resulted in two phenotypes that differ in their behavioural and neurochemical responses to addictive drugs, including morphine. To compare the ability of these lines to develop behavioural sensitization to morphine, female RHA and RLA rats were treated twice daily with either saline or escalating doses of morphine (5, 10, and 20 mg/kg, s.c. on the 1st, 2nd, and 3rd day of treatment, respectively), and were challenged with morphine (0.5 or 2 mg/kg, s.c) 1 day before and 3 weeks after repeated morphine administration. The locomotor activation produced by either challenge dose of morphine was more pronounced in RHA rats repeatedly treated with morphine vs the respective saline-treated controls, whereas no significant change in locomotor activity was observed in RLA rats. The results show that behavioral sensitization to morphine was induced in RHA but not in RLA rats
Chronic treatment with SCH 23390 increases the production rate of dopamine D1 receptors in the nigro-striatal system of the rat
No full textThe benzodiazepine recognition site inverse agonists Ro 15-4513 and FG 7142 both antagonize the EEG effects of ethanol in the rat.
No full textThe aim of the present study was to compare the ability of Ro 15-4513 and FG 7142, two inverse agonists for benzodiazepine recognition sites, to antagonize the EEG effects of ethanol in freely moving rats. Ethanol (2.5 g/kg, p.o.) induced sedation and ataxia associated with a progressive suppression of the fast cortical activities and an enhancement of low frequencies in both cortical and hippocampal tracings. In contrast, Ro 15-4513 (2 mg/kg, i.p.) and FG 7142 (10 mg/kg, i.p.) both caused a state of alertness associated with desynchronized cortical activity and theta hippocampal rhythm as well as spiking activity which was predominantly observed in the cortical tracings. When rats were treated with FG 7142 or RO 15-4513 either before or after ethanol, a reciprocal antagonism of the behavioral and EEG effects of ethanol and of the partial inverse agonists was observed. These data support the view that the anti-ethanol effects of Ro 15-4513 may be related to its partial inverse agonist properties
The depression-like behavior of roman low-avoidance rats in the porsolt test is normalized by subchronic and chronic desimipramine pre-treatments
No full textEffects of chronic antidepressant treatments in a putative genetic model of vulnerability (Roman low-avoidance rats) and resistance (Roman high-avoidance rats) to stress-induced depression
No full textIntroduction: The Roman low- (RLA) and high-avoidance (RHA) rats were selectively bred for, respectively, poor versus rapid acquisition of active avoidance in a shuttle box and, under aversive conditions, display reactive (RLA) versus proactive (RHA) coping behaviors. In the forced swim test (FST), RLA rats exhibit a depression-like behavior characterized by greater immobility and fewer climbing counts when compared with their RHA counterparts. Furthermore, subacute treatments with clinically effective antidepressant drugs decrease immobility and increase climbing or swimming in RLA rats but do not modify the performance of RHA rats. Objective and methods: Because chronic treatment with antidepressants is usually required to produce clinical effects, the present study was designed to compare the behaviors of RLA and RHA rats in the FST after subacute (1 day) and chronic (15 days) administration of desipramine, fluoxetine, and chlorimipramine. Results: In RLA rats, subacute treatments with low doses of desipramine, fluoxetine, and chlorimipramine (2.5-5 mg/kg) were ineffective whereas chronic treatments with the same doses of all three antidepressants decreased immobility and also increased climbing (desipramine) or swimming (fluoxetine). By contrast, neither subacute nor chronic treatments with these antidepressants induced significant changes in the behavior of RHA rats in the FST. Conclusions: RLA and RHA rats represent two divergent phenotypes, respectively susceptible and resistant to develop depression-like behavior under aversive environmental conditions that may be used to identify genetically determined neural substrates and mechanisms underlying vulnerability and resistance to stress-induced depression
Dissociation between cortical dopamine and serotonin output and fear-like behaviors in two lines of rats that display different coping strategies in response to stress
No full textDifferential activation of dopamine release in the nucleus accumbens core and shell after acute or repeated amphetamine injections: A comparative study in the Roman high- and low-avoidance rat lines
No full textThe selectively bred Roman high- and low-avoidance rats differ in emotionality and responsiveness to the motor effects of acute and repeated psychostimulant administration. These lines also show drastic differences in the neurochemical responses of their mesolimbic dopamine systems to addictive drugs. The nucleus accumbens is critically involved in the locomotor activation produced by psychostimulants and in the augmentation of this effect observed upon repeated drug administration (i.e. behavioral sensitization), although there is not a general consensus as to whether the nucleus accumbens-core or the nucleus accumbens-shell is preferentially involved in such alterations. This study was designed to evaluate the effects of acute amphetamine (0.20 mg/kg, s.c.) on dopamine output in the nucleus accumbens-shell and nucleus accumbens-core of the Roman lines under basal conditions (i.e. naive rats) and after the repeated administration of amphetamine (1 mg/kg, s.c.x 10 days) or saline. We show that (1) in naive rats, amphetamine caused a larger increment in dopamine output in the nucleus accumbens-shell vs the nucleus accumbens-core only in the Roman high-avoidance line; (2) repeated amphetamine elicits behavioral sensitization in Roman high-avoidance, but not Roman low-avoidance, rats; (3) in sensitized Roman high-avoidance rats, amphetamine provokes a larger increment in dopamine output in the nucleus accumbens-core, and an attenuated doparninergic response in the nucleus accumbens-shell, as compared with Roman high-avoidance rats repeatedly treated with saline; and (4) such neurochemical changes are not observed in the mesoaccumbens dopaminergic system of the sensitization-resistant Roman low-avoidance line. We propose that (1) Roman high-avoidance and Roman low-avoidance rats differ in the vulnerability to develop psychostimulant sensitization, (2) the nucleus accumbens-core and nucleus accumbens-shell subserve distinct functional roles in this phenomenon, and (3) comparative studies in the Roman lines may provide insight into the influence of neural substrates and genetic background on the individual vulnerability to addiction
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