Is there tonic activity in the endogenous opioid systems? A c-Fos study in the rat central nervous system after intravenous injection of naloxone or naloxone-methiodide

Gestreau, Christian; Guen, Stéphanie Le; Besson, Jean‐Marie

doi:10.1002/1096-9861(20001113)427:2<285::aid-cne9>3.0.co;2-t

Cited by 44 publications

(42 citation statements)

References 101 publications

(131 reference statements)

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“…In the case of nicotine-induced increases in BP, this 'deactivation' of neurotransmission would require that considerable endogenous opioid tone would be present in the denicotinized smoking condition. Although this was not directly investigated in the present report, substantial baseline endogenous opioid tone has been described in the rodent basal ganglia (Zangen et al, 1999) and amygdala (Kraus et al, 1996;Gestreau and Besson, 2000). Consistent with the presence of this tone in human subjects, the opioid receptor antagonist naloxone increased the activity of a number of cortical (eg anterior cingulate, prefrontal and insular, entorhinal and parahippocampal cortices) and subcortical (eg basal ganglia, hippocampus) regions in a recent fMRI study (Borras et al, 2004).…”

Section: Discussionsupporting

confidence: 65%

Smoking Modulation of μ-Opioid and Dopamine D2 Receptor-Mediated Neurotransmission in Humans

Scott

Domino

Heitzeg

et al. 2006

Neuropsychopharmacol

112

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This is a pilot examination of the hypothesis that some of the effects of smoking cigarettes in humans are mediated through nicotine activation of opioid and dopamine (DA) neurotransmission. Neuroimaging was performed using positron emission tomography and the radiotracers [11 C]carfentanil and [ 11 C]raclopride, labeling m-opioid and DA D2 receptors, respectively. Six healthy male smokers were abstinent overnight. After radiotracer administration, subjects smoked two denicotinized cigarettes, followed 45 min later by two average nicotine cigarettes. Dynamic data were acquired over 90 min, and transformed into parametric maps of receptor availability in vivo (binding potential, BP), corresponding to low and high nicotine smoking periods and analyzed on a voxel-by-voxel basis using SPM'99 and correction for multiple comparisons. Significant activation of m-opioid receptor-mediated neurotransmission from denicotinized to average nicotine conditions was observed in the right anterior cingulate cortex. DA D2 neurotransmission was activated in the ventral basal ganglia, correlating with Fagerströ m scale nicotine dependence scores. Lower m-opioid receptor BP was also detected during the denicotinized smoking condition in the smoker group, compared to baseline scans in non-smokers, in the cingulate cortex, thalamus, ventral basal ganglia, and amygdala. These reductions were reversed during the average nicotine condition in the thalamus, ventral basal ganglia and amygdala. These data point to both the feasibility of simultaneously examining opioid and DA neurotransmission responses to smoking in humans, as well as to the need to examine non-nicotine aspects of smoking to more fully understand the behavioral effects of this drug.

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Section: Discussionsupporting

confidence: 65%

Smoking Modulation of μ-Opioid and Dopamine D2 Receptor-Mediated Neurotransmission in Humans

Scott

Domino

Heitzeg

et al. 2006

Neuropsychopharmacol

112

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“…Morphine withdrawal was precipitated by subcutaneous injections of 120 g/kg naloxone hydrochloride (RBI/Sigma-Aldrich, Saint Quentin Fallavier, France) dissolved in isotonic saline (the naloxone dose was expressed as free base, 1 mg of naloxone base ϭ 1.113 mg of naloxone hydrochloride). Note that this naloxone dose has previously been shown to be without effect on both place aversion conditioning and Fos expression in placebo control rats (Gestreau et al, 2000;Hamlin et al, 2001;Frenois et al, 2002).…”

Section: Animals and Treatmentsmentioning

confidence: 80%

A Specific Limbic Circuit Underlies Opiate Withdrawal Memories

Frenois

Stinus²,

Blasi³

et al. 2005

J. Neurosci.

109

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Compulsive drug-seeking behavior and its renewal in former drug addicts is promoted by several situations, among which reactivation of drug withdrawal memories plays a crucial role. A neural hypothesis is that such memories reactivate the circuits involved in withdrawal itself and promote a motivational state leading to drug seeking or taking. To test this hypothesis, we have analyzed the neural circuits and cell populations recruited when opiate-dependent rats are reexposed to stimuli previously paired with withdrawal (memory retrieval) and compared them with those underlying acute withdrawal during conditioning (memory formation). Using in situ hybridization for c-fos expression, we report here that reexposure to a withdrawal-paired environment induced conditioned c-fos responses in a specific limbic circuit, which can be partially dissociated from the structures involved in acute withdrawal. At the amygdala level, c-fos responses were doubly dissociated between the central and basolateral (BLA) nuclei, when comparing the two situations. Detailed phenotypical analyses in the amygdala and ventral tegmental area (VTA) show that specific subpopulations in the BLA are differentially involved in the formation and retrieval of withdrawal memories, and strikingly that a population of VTA dopamine neurons is activated in both situations. Together, this indicates that withdrawal memories can drive activity changes in specific neuronal populations of interconnected limbic areas known to be involved in aversive motivational processes. This first study on the neural substrates of withdrawal memories strongly supports an incentive-motivational view of withdrawal in opiate addiction that could be crucial in compulsive drug seeking and relapse.

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“…Therefore, the greater baseline GABAergic neurotransmission observed in MOR KO mice could be attributed to the lack of tonic inhibition on the GABAergic neurotransmission mediated through MOR. Tonic activation of opioid receptors has been suggested by studies showing that opioid receptor antagonists increase c-fos expression (a marker for increased neuronal activity) in CeA (Gestreau et al, 2000). The possibility of tonic inhibition of GABAergic neurotransmission is further supported by the finding that there is little or no disinhibitory effect of locally injected GABA A receptor antagonists into CeA (Sanders and Shekhar, 1995;Veinante and Freund-Mercier, 1998).…”

Section: Discussionmentioning

confidence: 95%

μ-Opioid Receptors Selectively Regulate Basal Inhibitory Transmission in the Central Amygdala: Lack of Ethanol Interactions

Kang-Park

Kieffer²,

Roberts³

et al. 2008

J Pharmacol Exp Ther

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Endogenous opioid systems are implicated in the actions of ethanol. For example, -opioid receptor (MOR) knockout (KO) mice self-administer less alcohol than the genetically intact counterpart wild-type (WT) mice (Roberts et al., 2000). MOR KO mice also exhibit less anxiety-like behavior than WT mice (Filliol et al., 2000). To investigate the neurobiological mechanisms underlying these behaviors, we examined the effect of ethanol in brain slices from MOR KO and WT mice using sharp-electrode and whole-cell patch recording techniques. We focused our study in the central nucleus of the amygdala (CeA) because it is implicated in alcohol drinking behavior and stress behavior. We found that the amplitudes of evoked inhibitory postsynaptic currents (IPSCs) or inhibitory postsynaptic potentials (IPSPs) were significantly greater in MOR KO mice than WT mice. In addition, the baseline frequencies of spontaneous and miniature GABA A receptor-mediated inhibitory postsynaptic currents were significantly greater in CeA neurons from MOR KO than WT mice. However, ethanol enhancements of evoked IPSP and IPSC amplitudes and the frequency of miniature IPSCs were comparable between WT and MOR KO mice. Baseline spontaneous and miniature excitatory postsynaptic currents (EPSCs) and ethanol effects on EPSCs were not significantly different between MOR KO and WT mice. Based on knowledge of CeA circuitry and projections, we hypothesize that the role of MORand GABA receptor-mediated mechanisms in CeA underlying reinforcing effects of ethanol operate independently, possibly through pathway-specific responses within CeA.The endogenous opioid peptide system is implicated in ethanol reinforcement and dependence. Behavioral studies show that block of endogenous opioid action using naltrexone, a nonselective opioid antagonist, diminishes ethanol consumption (Herz, 1997), and this antagonist is currently used in the treatment of alcohol dependence in humans (Froehlich, 1996). However, the cellular mechanism underlying the interaction between endogenous opioids and ethanol for the reinforcing effects of ethanol is not yet clearly understood. Pharmacological studies using subtype-specific antagonists show that the key element in opioid peptide systems for the positive reinforcing effects of ethanol is the MOR (Ciccocioppo et al., 2002;Mhatre and Holloway, 2003). Genetically engineered mice without MOR consistently show decreased ethanol consumption compared with WT mice (Roberts et al., 2000). In addition, MOR KO mice show less anxiety-like behavior than WT mice (Filliol et al., 2000), suggesting an interaction between anxiety and ethanol

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Is there tonic activity in the endogenous opioid systems? A c-Fos study in the rat central nervous system after intravenous injection of naloxone or naloxone-methiodide

Cited by 44 publications

References 101 publications

Smoking Modulation of μ-Opioid and Dopamine D2 Receptor-Mediated Neurotransmission in Humans

Smoking Modulation of μ-Opioid and Dopamine D2 Receptor-Mediated Neurotransmission in Humans

A Specific Limbic Circuit Underlies Opiate Withdrawal Memories

μ-Opioid Receptors Selectively Regulate Basal Inhibitory Transmission in the Central Amygdala: Lack of Ethanol Interactions

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