1,721,042 research outputs found
Dopamine and serotonin release in dorsal striatum and nucleus accumbens is differentially modulated by morphine in DBA/2J and C57BL/6J mice
No full textNumerous studies have demonstrated that genetic factors significantly influence opioid ability to induce behavioral modification in mice. This differential sensitivity has been extensively studied, particularly in the DBA/2J and C57BL/6J strains. In the present study, using the "in vivo" microdialysis technique in these strains, we investigated the effect of morphine administration on the extracellular levels of dopamine (DA), serotonin (5-HT), and their metabolites in the nucleus accumbens and dorsal striatum-areas thought to be involved in morphine-induced locomotor hyperactivity. In the nucleus accumbens, morphine (20 mg/kg) significantly increased extracellular levels of DA in both strains. However, in dorsal striatum the morphine-induced increase of extracellular DA was lower in DBA/2J mice than in C57BL/6J. Moreover, morphine significantly stimulated 5-HT and 5-hydroxyindolacetic acid (5-HIAA) release both in nucleus accumbens and dorsal striatum of C57BL/6J mice, whereas it decreased 5-HT release without modifying 5-HIAA levels in DBA/2J mice. These results suggest that the different behavioral and biochemical responses to acute morphine described in these two strains could be mediated by different sensitivity of both the dopaminergic and the serotonergic systems
The CB1 receptor antagonist AM251 blocks drug-induced reinstatement of nicotine conditioned place preference in rats
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Adolescent THC exposure and vulnerability to drug abuse: Sex differences
No full textSeveral evidence suggests that the use of cannabis, during adolescence might lead to neurobiological changes that can affect adult brain functions and behavior (Realini et al., 2009). Biochemical and behavioral data from our research group showed that exposure to cannabinoid during adolescence in male rats produces an increased vulnerability to cannabinoids and heroin but not to nicotine intake in adulthood (unpublished data). In keeping with epidemiological data in humans, differences between the two sexes in drug seeking and intake have been well-documented in animal studies (Becker and Hu, 2008), with most recent findings related to abuse of cannabinoids (Fattore et al., 2010). Clinical and preclinical findings indicate that sex and gonadal hormones may account for individual differences in susceptibility to the reinforcing effects of addictive substances, and that differences in vulnerability to drug abuse may be mediated by the same biological mechanisms (Fattore et al., 2009). The aim of this study was to evaluate if cannabis exposure during adolescence was able to induce neurobiological changes not only in male but also in female rats, by investigating whether exposure to THC may increase the reinforcing effects of drugs of abuse, such as nicotine, heroin and cannabinoids in adulthood, in order to identify possible sex-specific differences. To this end, behavioral studies have been conducted on female rats using the chronic intravenous self-administration (IVSA) procedure in rats. Results were then compared to those obtained previously in our laboratory on male rats. Female adolescent Sprague-Dawley (for nicotine and heroin studies) and Lister Hooded rats (for WIN55,212-2 studies) (Deiana et al., 2007) at 35 postnatal day (PND) were treated intraperitoneally with increasing doses of THC (2.5, 5 and 10 mg/kg) or with cannabinoid vehicle twice/day for 11 consecutive days. Once animals reached the adulthood (75 PND), we studied the effects of THC exposure on acquisition of nicotine (30 μg/kg/infusion), heroin (30 μg/kg/infusion) and the cannabinoid agonist WIN55,212-2 (12.5 μg/kg/infusion) intravenous self-administration behavior using a continuous-reinforcement (fixed-ratio, FR-1) schedule of reinforcement. Faster acquisition and higher rate of drug intake was considered as index of vulnerability to drug abuse. Data from nicotine self-administration in female rats showed no significant difference between rats exposed and not-exposed (control) to THC during adolescence. On the other hand, THC adolescence exposure increased both heroin and WIN55,212-2 intake as compared to corresponding control groups. Altogether, these results seem to support the hypothesis that adolescence exposure to THC increases the vulnerability to heroin and cannabinoid, but not to nicotine, abuse in adult females. Comparison of results obtained in females with those observed in male rats shows that the average intake of drugs during the last ten days of self-administration training is significantly higher in females than in males. This increased vulnerability of female rats to drug taking as compared to males is in line with previous studies on sex-dependent differences showing that females are more sensitive than males to cannabinoid-induced behavioral effect
Modeling Anorexia Nervosa
No full textAlthough the pathophysiology underlying anorexia nervosa (AN) has not been fully elucidated, inflammation appears to be a critical component of its course and progression. Eicosanoids (eiCs) are bioactive signaling lipids primarily derived from arachidonic acid which have gained considerable biological relevance for their involvement in central and peripheral inflammatory processes. They were first described as pro-inflammatory mediators, and only afterward their anti-inflammatory and pro-resolution activities were also highlighted. Recent findings suggest that alterations in eiCs signaling could contribute to the dysregulated inflammatory status observed in AN. In this chapter we will first overview the most important immunological functions of the eiCs, including the regulation of neuroinflammatory processes, and then we will summarize the current knowledge on their possible implication in the pathophysiology of AN, with a focus on animal models
CB1 agonist administration modify 5-HT release in the nucleus accumbens and striatum of freely moving rats
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Antibody conjugates in neuroblastoma: a step forward in precision medicine
Full text linkNeuroblastoma (NB) is a pediatric cancer that often manifests in a high-risk form and is characterized by frequent relapses and resistance to conventional therapies. This underscores the urgent need for more effective and targeted treatment strategies. One promising avenue has been the identification of unique or overexpressed surface antigens on neoplastic cells, which has facilitated the development of antibody conjugates and related technologies. These include antibody-drug conjugates (ADCs) and immunotoxins (ITs), which deliver cytotoxic agents directly to tumor cells, as well as antibody-fluorophore conjugates (AFCs), which bind to surface antigens with high specificity to target malignant tumors. Additionally, radioimmunotherapy (RIT) allows the precise delivery of radioactive isotopes linked to a monoclonal antibody directly to the tumor cells. ADCs, ITs, and RIT represent a novel class of anti-cancer agents offering precision therapy with reduced systemic toxicity, enabling longer and potentially more effective treatment regimens. Meanwhile, AFCs are valuable tools in diagnostics, aiding in detecting and characterizing malignant tissues. Despite advancements in antibody conjugates for NB, significant challenges persist, including optimizing payload delivery, mitigating off-target effects, and addressing tumor heterogeneity. Future research should also prioritize refining and integrating these technologies into multimodal treatment protocols to improve outcomes for pediatric NB patients
Cannabinoids and reward: Interactions with the opioid system
No full textThere is currently substantial evidence that Cannabis sativa derivates act on brain reward in a way very similar to other drugs of abuse and exert numerous pharmacological effects through their interaction with various neurotransmitters and neuromodulators. Among them, the endogenous opioids seem to play an important role in modulating the addictive properties of cannabinoids. Given the plethora of research activity on such a topic, this brief review is necessarily focused on cannabinoid/opioid interaction in reward-related events and restricted to the recent literature. Recent findings from our and other laboratories concerning cannabinoid reinforcing effects as revealed by behavioral animal models of addiction are here summarized. Evidence is then provided demonstrating a functional cross-talk between the cannabinoid and opioid systems in the mutual modulation of the addictive behavior; accordingly, very recent data from transgenic mice lacking either the cannabinoid CB1 or opioid receptors are also presented. Finally, the role of the endogenous cannabinoid system in relapse to opioids is investigated by means of extinction/reinstatement animal models following a period, even prolonged, of drug abstinence. Altogether, the reviewed studies provided a better understanding of the neurobiological mechanisms involved in cannabinoid actions and revealed a bidirectional interaction between the endogenous cannabinoid and opioid systems in reward that extends to central mechanisms underlying relapsing phenomena. Challenges for the future involve elucidation of the neuroanatomical substrates of cannabinoids action, even in light of the therapeutic potential of these compounds
Behavioural and neurochemical assessment of salvinorin A abuse potential in the rat
No full textSalvinorin A is a recreational drug derived from Salvia divinorum, a sage species long used as an entheogen. While salvinorin A has potent hallucinogenic properties, its abuse potential has not been assessed consistently in controlled behavioural and neurochemical studies in rodents.
OBJECTIVE:
This study aimed to assess salvinorin A abuse potential by measuring its capacity to establish and maintain self-administration behaviour and to modify dopamine (DA) levels in the nucleus accumbens (NAcc) of rats.
RESULTS:
Male Lister Hooded (LH) and Sprague-Dawley (SD) rats were allowed to self-administer salvinorin A (0.5 or 1.0 μg/kg/infusion) intravenously 2 h/day for 20 days under a continuous schedule of reinforcement and lever pressing as operandum. LH rats discriminated between the active and inactive levers but did not reach the acquisition criterion for stable self-administration (≥12 active responses vs ≤5 inactive responses for at least 5 consecutive days). SD rats discriminated between the two levers at the lower dose only but, like LH rats, never acquired stable self-administration behaviour. Systemic salvinorin A increased extracellular DA in the NAcc shell of both LH (at ≥40 μg/kg) and SD rats (at ≥5 μg/kg), but injection into the ventral tegmental area (VTA) induced no significant change in NAcc DA concentration in LH rats and only brief elevations in SD rats.
CONCLUSIONS:
Salvinorin A differs from other commonly abused compounds since although it affects accumbal dopamine transmission, yet it is unable, at least at the tested doses, to sustain stable intravenous self-administration behaviour
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