Cocaine counteracts LPS-induced hypolocomotion and triggers locomotor sensitization expression

Tortorelli, Lucas Silva; Engelke, Douglas Senna; Lunardi, Paula; Souza, Tadéu Mello e; Santos-Junior, Jair Guilherme; Gonçalves, Carlos-Alberto

doi:10.1016/j.bbr.2015.03.054

Cited by 10 publications

(12 citation statements)

References 25 publications

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“…Findings of drug sensitization after TBI have been reported before (Lowing et al ., ), however, this was with regard to the sedative effects of ethanol. Further, it has been shown that inflammatory challenge, outside of injury events, can lead to sensitization to the effects of cocaine (Tortorelli et al ., ). These data, taken together, suggest that a high level of sensitization to the effects of cocaine could actually lead to aversion, and may potentially explain some of the differences in acquisition in the current study.…”

Section: Discussionmentioning

confidence: 99%

Cocaine self‐administration is increased after frontal traumatic brain injury and associated with neuroinflammation

Haar

Ferland

Kaur

et al. 2018

Eur J of Neuroscience

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Traumatic brain injury (TBI) has been linked to the development of numerous psychiatric diseases, including substance use disorder. However, it can be difficult to ascertain from clinical data whether the TBI is cause or consequence of increased addiction vulnerability. Surprisingly few studies have taken advantage of animal models to investigate the causal nature of this relationship. In terms of a plausible neurobiological mechanism through which TBI could magnify the risk of substance dependence, numerous studies indicate that TBI can cause widespread disruption to monoaminergic signaling in striatal regions, and also increases neuroinflammation. In the current study, male Long-Evans rats received either a mild or severe TBI centered over the frontal cortex via controlled cortical impact, and were subsequently trained to self-administer cocaine over 10 6-hour sessions. At the end of the study, markers of striatal dopaminergic function, and levels of inflammatory cytokine levels in the frontal lobes, were assessed via western blot and multiplex ELISA, respectively. There was significantly higher cocaine intake in a subset of animals with either mild or severe TBI. However, many animals within both TBI groups failed to acquire self-administration. Principal components analysis suggested that both dopaminergic and neuroinflammatory proteins were associated with overall cocaine intake, yet only an inflammatory component was associated with acquisition of self-administration, suggesting neuroinflammation may make a more substantial contribution to the likelihood of drug-taking. Should neuroinflammation play a causal role in mediating TBI-induced addiction risk, anti-inflammatory therapy may reduce the likelihood of substance abuse in TBI populations.

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Section: Discussionmentioning

confidence: 99%

Cocaine self‐administration is increased after frontal traumatic brain injury and associated with neuroinflammation

Haar

Ferland

Kaur

et al. 2018

Eur J of Neuroscience

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“…24 Mice acutely pre-treated with LPS and cocaine displayed greater locomotion in a behavioral task compared to pre-treatment with cocaine alone. 51 In nonhuman primates, 2 weeks of IFNα (a cytokine involved in inflammatory signaling) caused an increase in amphetamine-stimulated DA release over amphetamine alone. 25 Our findings are consistent with prior studies, namely, stimulated DA elevation was enhanced with an acute dose of LPS compared to placebo.…”

Section: Discussionmentioning

confidence: 99%

Systemic inflammation enhances stimulant-induced striatal dopamine elevation

et al. 2017

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Changes in the mesolimbic dopamine (DA) system are implicated in a range of neuropsychiatric conditions including addiction, depression and schizophrenia. Dysfunction of the neuroimmune system is often comorbid with such conditions and affects similar areas of the brain. The goal of this study was to use positron emission tomography with the dopamine D2 antagonist tracer, 11C-raclopride, to explore the effect of acute immune activation on striatal DA levels. DA transmission was modulated by an oral methylphenidate (MP) challenge in order to reliably elicit DA elevation. Elevation in DA concentration due to MP was estimated via change in 11C-raclopride binding potential from the baseline scan. Prior to the post-MP scan, subjects were pre-treated with either the immune activator lipopolysaccharide (LPS) or placebo (PBO) in a cross-over design. Immune activation was confirmed by measuring tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and IL-8 concentration in plasma. Eight healthy subjects were scanned four times each to determine the MP-induced DA elevation under both LPS and PBO pre-treatment conditions. MP-induced DA elevation in the striatum was significantly greater (P<0.01) after LPS pre-treatment compared to PBO pre-treatment. Seven of eight subjects responded similarly. This effect was observed in the caudate and putamen (P<0.02), but was not present in ventral striatum. DA elevation induced by MP was significantly greater when subjects were pre-treated with LPS compared to PBO. The amplification of stimulant-induced DA signaling in the presence of systemic inflammation may have important implications for our understanding of addiction and other diseases of DA dysfunction.

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“…Behavioral sensitization refers to a phenomenon characterized by enhanced responsiveness following repeated, intermittent treatment with psychomotor stimulants (12,13). Locomotor activity, as a measure of spontaneous behavior, has been primarily assessed in behavioral sensitization studies (14,15). Additionally, behavioral sensitization has been established in rodents that have repeatedly been administered the same or incremental doses of a drug (16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Huperzine A inhibits immediate addictive behavior but not behavioral sensitization following repeated morphine administration in rats

Sun

Tian

Cui

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Acetylcholinesterase inhibitors are regarded as promising therapeutic agents to treat addiction. The current study aimed to examine the effects of huperzine A, a cholinesterase inhibitor, on behavioral sensitization induced by repeated morphine administration and relapse induced by contextual conditioning. The present study also assessed whether the state-dependency hypothesis may explain the results. Adult rats were divided into four groups (n=8) and intraperitoneally injected with 0.2, 0.3 or 0.4 mg/kg huperzine A or saline (1 ml/kg, control), for 5 days. The effect of repeated huperzine A administration alone on locomotor activity was assessed. For the experiments that analyzed the development of morphine-induced sensitization, 40 rats were divided into five groups (n=8): Saline+Saline, Saline+Morphine, 0.2, 0.3 and 0.4 mg/kg huperzine A+Morphine. Following a withdrawal period of 7 days, all animals were administered saline or morphine, as appropriate. To test the state-dependency hypothesis, the rats in the Saline+Morphine group were injected with saline and morphine, while the other three groups were administered different doses of huperzine A and morphine. To examine the effect of huperzine A on the expression of morphine-induced sensitization, the rats in huperzine A+Morphine groups were injected with appropriate concentrations of huperzine A, and morphine. The current results indicated that the administration of huperzine A alone did not affect locomotor activity, while higher doses of huperzine A inhibited the addictive behavior induced by morphine at the development phase. Additionally, huperzine A administration during the expression phase of morphine sensitization did not inhibit the relapse induced by administration of saline.Furthermore, 0.4 mg/kg huperzine A inhibited the expression of morphine-induced behavioral sensitization. Therefore, the results of the current study do not support the state-dependency hypothesis.

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Cocaine counteracts LPS-induced hypolocomotion and triggers locomotor sensitization expression

Cited by 10 publications

References 25 publications

Cocaine self‐administration is increased after frontal traumatic brain injury and associated with neuroinflammation

Cocaine self‐administration is increased after frontal traumatic brain injury and associated with neuroinflammation

Systemic inflammation enhances stimulant-induced striatal dopamine elevation

Huperzine A inhibits immediate addictive behavior but not behavioral sensitization following repeated morphine administration in rats

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