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DIFFERENTIAL RESPONSIVENESS OF NUCLEUS ACCUMBENS DOPAMINE TO STIMULI INSTRUMENTALLY CONDITIONED TO CONVENTIONAL OR DRUG REINFORCERS
No full textAdolescent Cannabis exposure differentially affects Heroin Reinforcement and Accumbens Dopamine transmission in Lewis and Fisher344 rats
No full textBackground: Vulnerability to drug addiction depends on acquired as well as genetic factors (Swendsen & Le Moal 2010). Among acquired factors is previous exposure to other drugs of abuse. Thus, exposure to Cannabis has been suggested to predispose to heroin abuse and dependence (Gateway Hypothesis) (Kandel et al. 2006). Here we studied the influence of adolescent delta 9-THC exposure on heroin reward and renforcement and on the in vivo dopamine stimulant properties of heroin in two inbred rat strains differentially vulnerable to drugs of abuse, the addiction prone Lewis and the addiction resistant Fisher344 strain.
Results: THC increased extracellular DA, as estimated by microdialysis, in Lewis but not in Fischer 344 rats. Adolescent THC exposure potentiated DA stimulant effects of heroin in the shell and core of Lewis and only in the core of Fischer344 rats. Control Lewis rats developed stronger conditioned place preference (CPP) to heroin and resistance to extinction compared with Fischer344 strain. In Lewis rats, THC exposure did not increse heroin CPP but potentiated the effect of heroin priming. In Fischer344 rats, THC exposure increased heroin CPP and made it resistant to extinction. Lewis rats showed marked seeking reactions during extinction and hedonic reactions in response to heroin priming. THC pre-exposure increased responding for iv heroin self-administration on FR3 and FR5 and on progressive ratio 3-4 in Lewis but not in Fisher344 rats. After extinction, presentation of discriminative stimuli associated to drug availability on the active nose-poke as well as priming by passive heroin exposure, reinstated responding more effectively in Lewis rats pre-exposed to THC than in saline controls.
Conclusions: These observations suggest that, in genetically predisposed individuals, adolescent Cannabis exposure can increase vulnerability to heroin addiction by augmenting heroin reinforcing properties.
These studies were founded by the Dipartimento politiche antidroga, Presidenza del Consiglio, Ital
Differential neurochemical and behavioural effects of response-contingentand response-noncontingent cocaine exposure: Shell/core dopamine responsiveness and sensitization
No full textAdolescent Cannabis exposure differentially affects heroin reinforcement and accumbens dopamine transmission in Lewis and Fischer344 rats
No full textMonitoring extracellular dopamine in the rat nucleus accumbens shell and core during acquisition and maintenance of intravenous WIN 55,212-2 self-administration
No full textRationale WIN 55,212-2, a potent cannabinoid receptor 1 agonist, is self-administered by animals to evaluate abuse liability of cannabinoids, but to date no information is yet available about its effects on dopaminergic transmission during active response-contingent administration.
Objective This study monitored the changes of extracellular dopamine (DA) in the nucleus accumbens (NAc) shell and core during active intravenous WIN 55,212-2 self-administration (SA).
Methods Rats, implanted with a jugular catheter and bilateral intracerebral chronic cannulae, were trained for 3 weeks to self-administer WIN 55,212-2 (12.5 mu g/kg) in single daily 1-h sessions under a fixed ratio 1 (FR 1) schedule, than switched to FR 2 for a further week. During SA sessions, microdialysis assays were performed every 3rd day, and then daily starting from the 13th session. Dialysate DA from the NAc shell and core was monitored before, during, and for 30 min after SA.
Results Dialysate DA increased during WIN 55,212-2 SA starting from the 1st week in the NAc shell and on the 2nd week in the core. The increase of dialysate DA in the NAc shell was larger than that in the core on all weeks. Dialysate DA did not change during extinction sessions in spite of active nose poking.
Conclusions Response-contingent WIN 55,212-2 SA preferentially increases the NAc shell DA output as compared to that of the core independently from the duration of the WIN 55,212-2 exposure. Increase in NAc DA is strictly related to WIN 55,212-2 actions because it is not observed during extinction despite active responding
Striatal application of nicotine, but not of lobeline, attenuates dopamine release in freely moving rats
No full textWe investigated the physiological role of native low- and high-affinity nicotinic acetylcholine receptors (nAChRs) in regulating dopamine (DA) release from striatal DA terminals. To evaluate the functional interactions of the two receptor subtypes, nicotine (which interacts with both high- and low-affinity nAChRs) and lobeline (which selectively interacts with high-affinity nAChRs) were perfused through a microdialysis probe implanted into the striatum of freely moving rats. The DA content of successive dialysates was quantified by HPLC with an electrochemical detector. A short-lasting (1-min) perfusion of nicotine or lobeline dose-dependently increased the DA content of striatal dialysates. A second application of the same dose of nicotine resulted in an attenuated DA increase, compared with the increase elicited by the first application; however, the DA increase elicited by a second application of lobeline was similar to that of the first lobeline application. The nicotine-induced response was not attenuated when it followed a Lobeline perfusion; in contrast, if the nicotine perfusion preceded that of lobeline, the lobeline-induced response was attenuated. In the presence of mecamylamine (a noncompetitive nAChR antagonist), the increase in DA content of striatal dialysate samples induced by either nicotine or lobeline was attenuated. However, in the presence of methyllycaconitine (a preferential antagonist for low-affinity alpha homomeric nAChRs) the nicotine response was attenuated but that of lobeline was unaffected. These results suggest that the functional inactivation of striatal nAChRs requires the simultaneous activation of both low- and high-affinity nAChRs. Since lobeline is devoid of reinforcing properties, one might infer that the reinforcing properties of nicotine require the simultaneous activation of high- and low-affinity brain nAChRs
Reciprocal effects of response contingent and non-contingent intravenous heroin on in vivo nucleus accumbens shell versus core dopamine: a repeated sampling microdialysis study
No full textAccumbal shell and core dopamine responsiveness during operant responding for sucrose
No full textExperimental evidence indicates that accumbal dopamine (DA) is critically involved in the reward properties of food and drugs of abuse, that preferentially stimulate DA transmission in the nucleus accumbens (NAc) shell compare to the core. The involvement of the two NAc compartments in the responsiveness to conditioned stimuli (CS), linked with rewards (food, sex, drugs of abuse) (US), is debated. Much discrepancies exist about the impact of food CSs on mesolimbic DA transmission. In particular it has been reported that after classical conditioning paradigm NAc shell DA shows responsiveness to food US, but it is unresponsive to food CS, while NAc core and prefrontal cortex DA are both affected by food-CS and US.
Here we examined the changes of mesolimbic DA in the responsiveness to food CS and US.
Using microdialysis technique coupled with self administration paradigm, we have monitored DA transmission in NAc shell and core during: 1) sucrose pellets seeking behavior, 2) presentation of visual and auditory cues associated with primary stimulus and 3) non-contingent administration of sucrose pellets.
During our study we found that NAc shell DA has been activated not only by the conditioned cues but also by food after the instrumental conditioning, and that when both stimuli are presented in the same moment the increase of DA is strengthened and prolonged.
These results provide that DA in the NAc shell plays an important role on the acquisition and expression of motivated behavior in food consumption
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
Differential 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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