Ketamine increases striatal dopamine release and hyperlocomotion in adult rats after postnatal functional blockade of the prefrontal cortex

Usun, Yusuf; Eybrard, Séverine; Meyer, Francisca; Louilot, Alain

doi:10.1016/j.bbr.2013.08.017

Cited by 39 publications

(49 citation statements)

References 83 publications

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“…These ketamine-induced effects are mediated by both descending and ascending fibers projecting to the VTA (Morikawa and Paladini 2011). There is also a large body of evidence, gained via both in vivo and in vitro techniques, showing that ketamine increases DA release and blocks DA reuptake in the dorsal striatum (Keita et al 1996; Tso et al 2004; Usun et al 2013), nucleus accumbens (Hancock and Stamford 1999; Witkin et al 2016), and prefrontal cortex (Lindefors et al 1997; Lorrain et al 2003; see Smith et al 1981). In some cases, the ability of ketamine to modulate DA release is attributed to actions involving afferent inhibitory interneurons in DA target areas (Verma and Moghaddam 1996; Lorrain et al 2003; Usun et al 2013; see also Can et al 2016), while others suggest that ketamine acts as an indirect DA agonist (Irifune et al 1991; Nishimura et al 1998; Hancock and Stamford 1999).…”

Section: Introductionmentioning

confidence: 99%

Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose

et al. 2017

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Rationale Ketamine is used by preadolescent and adolescent humans for licit and illicit purposes. Objective The goal of the present study was to determine the effects of acute and repeated ketamine treatment on the unconditioned behaviors and conditioned locomotor activity of preadolescent and adolescent rats. Methods To assess unconditioned behaviors, female and male rats were injected with ketamine (5–40 mg/kg) and distance traveled was measured on PD 21–25 or PD 41–45. To assess conditioned activity, male and female rats were injected with saline or ketamine in either a novel test chamber or the home cage on PD 21–24 or PD 41–44. One day later, rats were injected with saline and conditioned activity was assessed. Results Ketamine produced a dose-dependent increase in the locomotor activity of preadolescent and adolescent rats. Preadolescent rats did not exhibit sex differences, but ketamine-induced locomotor activity was substantially stronger in adolescent females than males. Repeated ketamine treatment neither caused a day-dependent increase in locomotor activity nor produced conditioned activity in preadolescent or adolescent rats. Conclusions The activity-enhancing effects of ketamine are consistent with the actions of an indirect dopamine agonist, while the inability of ketamine to induce conditioned activity is unlike what is observed after repeated cocaine or amphetamine treatment. This dichotomy could be due to ketamine’s ability to both enhance DA neurotransmission and antagonize NMDA receptors. Additional research will be necessary to parse out the relative contributions of DA and NMDA system functioning when assessing the behavioral effects of ketamine during early ontogeny.

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Section: Introductionmentioning

confidence: 99%

Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose

et al. 2017

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“…Finally, recently obtained data showed that animals that underwent early-life inactivation of the prefrontal cortex also displayed greater behavioral and neurochemical reactivity to D-amphetamine (Meyer and Louilot, 2012) and ketamine, at subanesthetic doses (Usun et al, 2013). This is of particular interest given that both these drugs are known to induce psychotic symptoms in healthy individuals and to worsen such symptoms in patients with schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, results obtained in our laboratory, which are discussed in detail below, showed that neonatal transient TTX inactivation of the entorhinal cortex, ventral subiculum or prefrontal cortex induced disturbed dopaminergic and behavioral responses related to latent inhibition (LI) in adulthood (Peterschmitt et al, 2007; Meyer et al, 2009; Meyer and Louilot, 2011, 2012). It is important to note that no lesions or macroscopic anatomical changes have been observed in the aforementioned studies following neonatal TTX inactivation (Lipska et al, 2002; Peterschmitt et al, 2007; Meyer et al, 2009; Brooks et al, 2011; Meyer and Louilot, 2011, 2012; Brooks et al, 2012; Usun et al, 2013). Taken together, functional disconnection models appear to be a relevant conceptual approach to animal modeling for some aspects of the pathophysiology of schizophrenia and without inducing any major anatomical lesion.…”

Section: Introductionmentioning

confidence: 98%

Consequences at adulthood of transient inactivation of the parahippocampal and prefrontal regions during early development: new insights from a disconnection animal model for schizophrenia

Meyer

Louilot

2014

Front. Behav. Neurosci.

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The psychic disintegration characteristic of schizophrenia is thought to result from a defective connectivity, of neurodevelopmental origin, between several integrative brain regions. The parahippocampal region and the prefrontal cortex are described as the main regions affected in schizophrenia. Interestingly, latent inhibition (LI) has been found to be reduced in patients with schizophrenia, and the existence of a dopaminergic dysfunction is also generally well accepted in this disorder. In the present review, we have integrated behavioral and neurochemical data obtained in a LI protocol involving adult rats subjected to neonatal functional inactivation of the entorhinal cortex, the ventral subiculum or the prefrontal cortex. The data discussed suggest a subtle and transient functional blockade during early development of the aforementioned brain regions is sufficient to induce schizophrenia-related behavioral and dopaminergic abnormalities in adulthood. In summary, these results support the view that our conceptual and methodological approach, based on functional disconnections, is valid for modeling some aspects of the pathophysiology of schizophrenia from a neurodevelopmental perspective.

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“…This may imply that ketamine may have larger half maximal inhibitory (ID 50 ) when compared to the other two; however, it needs further investigations. The explanation could be that ketamine, as an NMDA noncompetitive antagonist, can inhibit the reuptake of dopamine and increase striatal dopamine release [28, 29]. Dopaminergic response induced by ketamine results in excess dopamine into the synaptic clefts of dopaminergic neurons and then reduces the specific binding of [ 18 F]FDOPA.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Inhibitory Effect of Recreational Drugs on Dopaminergic Terminal Neuron by PET and Whole-Body Autoradiography

Yeh

Lin

Kong

et al. 2014

BioMed Research International

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There is little investigation for the functional roles of peripheral dopamine. [18F]FDOPA has been used in cancer imaging (i.e., neuroendocrine and tumors pancreatic tumors) and neuroimaging (i.e., Parkinson's disease and Huntington's disease). Here, we accessed side effects of recreational drugs such as ketamine, cocaine, and methamphetamine on dopamine neurons in peripheral organs by using positron emission tomography (PET) imaging and quantitative whole-body autoradiography (QWBAR) with [18F]FDOPA. The images were applied for the measurement of specific binding ratios (SBRs) of striatum with the cerebellum as the reference region. Clear striatal [18F]FDOPA-derived radioactivity was observed. Moderate level of radiotracer accumulation was presented in the mucosal layers of the stomach and small intestine. The medulla layers of kidney had higher radioactivity than that of the cortex. Blocking images markedly eliminated the specific binding of [18F]FDOPA in the striatum and in peripheral organs such as stomachs, intestines, and kidney. Ketamine showed the highest inhibitory effect on striatal [18F]FDOPA-derived radioactivity followed by cocaine and methamphetamine. The current results demonstrated a useful crossing-validating tool that enhances the capability of [18F]FDOPA for further investigations of the alteration of dopaminergic neurons in the brain disorder or cancer diseases in peripheral tissues.

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Ketamine increases striatal dopamine release and hyperlocomotion in adult rats after postnatal functional blockade of the prefrontal cortex

Cited by 39 publications

References 83 publications

Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose

Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose

Consequences at adulthood of transient inactivation of the parahippocampal and prefrontal regions during early development: new insights from a disconnection animal model for schizophrenia

Evaluation of Inhibitory Effect of Recreational Drugs on Dopaminergic Terminal Neuron by PET and Whole-Body Autoradiography

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