Immunocytochemical localization of an imidazoline receptor protein in the central nervous system

Ruggiero, David A.; Regunathan, S.; Wang, H; Milner, Teresa A.; Reis, Donald J.

doi:10.1016/s0006-8993(97)01203-1

Cited by 73 publications

(45 citation statements)

References 55 publications

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“…Subsequent immunocytochemical mapping studies localized IAA-RP in neurons of numerous other brain regions, suggesting that its putative modulatory role is not limited to the brainstem (Friedrich et al 2007). In fact, IAA-RP immunoreactivity is prominent in both CA3 and CA1 pyramidal cells, and high densities of I-R binding sites are present in the hippocampus (De Vos et al 1994;Piletz et al 2000;Ruggiero et al 1998). The presence of IAA-RP in dendrites of CA1 cells raises the possibility that dendritic IAA-RP, if released (Bergquist and Ludwig 2008), could act presynaptically on the contacts formed by the Schaffer collaterals.…”

Section: Discussionmentioning

confidence: 99%

Imidazoleacetic acid-ribotide induces depression of synaptic responses in hippocampus through activation of imidazoline receptors

Bozdagi

Wang²,

Martinelli³

et al. 2011

Journal of Neurophysiology

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4-acetic acid-ribotide (IAA-RP), an endogenous agonist at imidazoline receptors (I-Rs), is a putative neurotransmitter/regulator in mammalian brain. We studied the effects of IAA-RP on excitatory transmission by performing extracellular and whole cell recordings at Schaffer collateral-CA1 synapses in rat hippocampal slices. Bathapplied IAA-RP induced a concentration-dependent depression of synaptic transmission that, after washout, returned to baseline within 20 min. Maximal decrease occurred with 10 M IAA-RP, which reduced the slope of field extracellular postsynaptic potentials (fEPSPs) to 51.2 Ϯ 5.7% of baseline at 20 min of exposure. Imidazole-4-acetic acid-riboside (IAA-R; 10 M), the endogenous dephosphorylated metabolite of IAA-RP, also produced inhibition of fEPSPs. This effect was smaller than that produced by IAA-RP (to 65.9 Ϯ 3.8% of baseline) and occurred after a further 5-to 8-min delay. The frequency, but not the amplitude, of miniature excitatory postsynaptic currents was decreased, and paired-pulse facilitation (PPF) was increased after application of IAA-RP, suggesting a principally presynaptic site of action. Since IAA-RP also has low affinity for ␣ 2 -adrenergic receptors (␣ 2 -ARs), we tested synaptic depression induced by IAA-RP in the presence of ␣ 2 -ARs, I 1 -R, or I 3 -R antagonists. The ␣ 2 -AR antagonist rauwolscine (100 nM), which blocked the actions of the ␣ 2 -AR agonist clonidine, did not affect either the IAA-RP-induced synaptic depression or the increase in PPF. In contrast, efaroxan (50 M), a mixed I 1 -R and ␣ 2 -AR antagonist, abolished the synaptic depression induced by IAA-RP and abolished the related increase in PPF. KU-14R, an I 3 -R antagonist, partially attenuated responses to IAA-RP. Taken together, these data support a role for IAA-RP in modulating synaptic transmission in the hippocampus through activation of I-Rs. presynaptic inhibition; hippocampal slice preparation; Schaffer collaterals

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Section: Discussionmentioning

confidence: 99%

Imidazoleacetic acid-ribotide induces depression of synaptic responses in hippocampus through activation of imidazoline receptors

Bozdagi

Wang²,

Martinelli³

et al. 2011

Journal of Neurophysiology

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“…However, based on the anatomical distribution of I1 and a2-adrenergic receptors (Ruggiero et al, 1998), and the fact that the ventral noradrenergic pathway is involved in the affective response to opiate withdrawal (Delfs et al, 2000), possible candidates include the NTS and the BNST. In fact, Ruggiero et al (1998) report a high expression of the imidazoline receptor protein in the NTS and BNST, especially in axon terminals, suggesting a possible role for these receptors in the regulation of neurotransmitter release. Further experiments examining, for example, the effect of microinjection of clonidine in the different brain regions are needed to establish which of these (or other) structures are the loci of the adrenergic/imidazolinergic interaction.…”

Section: Activation Of Da Neurons By Withdrawal After Clonidine F Geomentioning

confidence: 99%

“…In the brain the I1R has a unique distribution, partially overlapping that of a2R, and is most heavily concentrated in the nucleus tractus solitarius (NTS), BNST, and central amygdaloid nucleus. In contrast, I1Rs are not expressed in the locus coeruleus (LC) (King et al, 1995;Ruggiero et al, 1998). In the central nervous system the functions associated with imidazoline receptors are largely unknown but evidence exists for their involvement in the withdrawal syndrome resulting from chronic opiate abuse (Tierney et al, 1988) as well as in major depression and neurodegenerative diseases (for a review see GarciaSevilla et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

Georges

Aston‐Jones

2003

Neuropsychopharmacol

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The a2 adrenoceptor (a2R) agonist clonidine is used as a treatment for heroin addiction. Substantial evidence indicates that dopaminergic and noradrenergic systems have key roles in opiate dependence and withdrawal but the possible interactions between these two pathways remain unclear. The objective of this study was to establish the effects of clonidine pretreatment on ventral tegmental area dopaminergic (VTA DA) neuronal activity during morphine withdrawal. Responses of VTA DA neurons to withdrawal precipitated by naltrexone were characterized in anesthetized rats using extracellular recordings. As expected, withdrawal produced a marked inhibition of VTA DA neuronal activity. However, pretreatment with clonidine prevented this inhibition induced by withdrawal, and instead produced a long-lasting activation of firing rate (+50%) and burst firing (+19%). In contrast, pretreatment with a more selective a2R agonist, UK14304, did not prevent the inhibition of VTA DA neuron activity during withdrawal. We tested whether the high affinity of clonidine for imidazoline-1 receptors (I1Rs) was responsible for the difference between these two a2R agonists. In morphine-dependent rats pretreated with rilmenidine (mixed a2R/I1R agonist), precipitation of withdrawal elicited a 22% increase of VTA DA impulse activity. The action of clonidine on I1Rs was studied by coadministering clonidine with RX821002, a specific a2R antagonist. Pretreatment with RX821002 plus clonidine prevented the inhibition of VTA DA activity during withdrawal but failed to produce excitation. These results indicate that the pharmacological effects of clonidine on VTA DA neurons during morphine withdrawal is related to actions on I1Rs as well as a2Rs.

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“…Recently, agmatine has been shown to prevent or attenuate tolerance to morphine and other opioid agonists (Kolesnikov et al, 1996), thus suggesting a possible implication of the imidazoline receptor system on the modulation of opioid antinociception and tolerance. The presence of imidazoline receptors also has been detected in brain areas involved in the perception and responses to pain (Ruggiero et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…According to dierences in their pharmacological pro®les, tissue and subcellular distributions, imidazoline receptors have been classi®ed into two main types: I 1 -and I 2 -imidazoline receptors (Michel & Insel, 1989;Ernsberger, 1992). The I 2 -imidazoline receptors are widely distributed and in the brain are expressed on neurones, but mainly on glial cells (Regunathan et al, 1993;Olmos et al, 1994;Ruggiero et al, 1998). The amine agmatine (decarboxylated arginine) has been proposed as an endogenous agonist at imidazoline receptors (Li et al, 1994) and to act as a neurotransmitter or neuromodulator for some members of this receptor family (Li et al, 1994;Piletz et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Attenuation of tolerance to opioid‐induced antinociception and protection against morphine‐induced decrease of neurofilament proteins by idazoxan and other I₂‐imidazoline ligands

Boronat

Olmos

Garcı́a-Sevilla

1998

British J Pharmacology

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1 Agmatine, the proposed endogenous ligand for imidazoline receptors, has been shown to attenuate tolerance to morphine-induced antinociception (Kolesnikov et al., 1996). The main aim of this study was to assess if idazoxan, an a 2 -adrenoceptor antagonist that also interacts with imidazoline receptors, could also modulate opioid tolerance in rats and to establish which type of imidazoline receptors (or other receptors) are involved. 2 Antinociceptive responses to opioid drugs were determined by the tail-¯ick test. The acute administration of morphine (10 mg kg 71 , i.p., 30 min) or pentazocine (10 mg kg 71 , i.p., 30 min) resulted in marked increases in tail-¯ick latencies (TFLs). As expected, the initial antinociceptive response to the opiates was lost after chronic (13 days) treatment (tolerance). When idazoxan (10 mg kg 71 , i.p.) was given chronically 30 min before the opiates it completely prevented morphine tolerance and markedly attenuated tolerance to pentazocine (TFLs increased by 71 ± 143% at day 13). Idazoxan alone did not modify TFLs. 3 The concurrent chronic administration (10 mg kg 71 , i.p., 13 days) of 2-BFI, LSL 60101, and LSL 61122 (valldemossine), selective and potent I 2 -imidazoline receptor ligands, and morphine (10 mg kg 71 , i.p.), also prevented or attenuated morphine tolerance (TFLs increased by 64 ± 172% at day 13). This attenuation of morphine tolerance was still apparent six days after discontinuation of the chronic treatment with LSL 60101-morphine. The acute treatment with these drugs did not potentiate morphineinduced antinociception. These drugs alone did not modify TFLs. Together, these results indicated the speci®c involvement of I 2 -imidazoline receptors in the modulation of opioid tolerance. The potencies of the imidazolines idazoxan, RX821002 and moxonidine were similar, indicating a lack of relationship between potency on NMDA receptors and ability to attenuate opioid tolerance. These results suggested that modulation of opioid tolerance by idazoxan is not related to NMDA receptors blockade. 6 Chronic treatment (13 days) with morphine (10 mg kg 71 , i.p.) was associated with a marked decrease (49%) in immunolabelled neuro®lament proteins (NF-L) in the frontal cortex of morphine-tolerant rats, suggesting the induction of neuronal damage. Chronic treatment (13 days) with idazoxan (10 mg kg 71 ) and LSL 60101 (10 mg kg 71 ) did not modify the levels of NF-L proteins in brain. Interestingly, the concurrent chronic treatment (13 days) of idazoxan or LSL 60101 and morphine, completely reversed the morphine-induced decrease in NF-L immunoreactivity, suggesting a neuroprotective role for these drugs. 7 Together, the results indicate that chronic treatment with I 2 -imidazoline ligands attenuates the development of tolerance to opiate drugs and may induce neuroprotective eects on chronic opiate treatment. Moreover, these ®ndings oer the I 2 -imidazoline ligands as promising therapeutic coadjuvants in the management of chronic pain with opiate drugs.

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Immunocytochemical localization of an imidazoline receptor protein in the central nervous system

Cited by 73 publications

References 55 publications

Imidazoleacetic acid-ribotide induces depression of synaptic responses in hippocampus through activation of imidazoline receptors

Imidazoleacetic acid-ribotide induces depression of synaptic responses in hippocampus through activation of imidazoline receptors

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

Attenuation of tolerance to opioid‐induced antinociception and protection against morphine‐induced decrease of neurofilament proteins by idazoxan and other I₂‐imidazoline ligands

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Immunocytochemical localization of an imidazoline receptor protein in the central nervous system

Cited by 73 publications

References 55 publications

Imidazoleacetic acid-ribotide induces depression of synaptic responses in hippocampus through activation of imidazoline receptors

Imidazoleacetic acid-ribotide induces depression of synaptic responses in hippocampus through activation of imidazoline receptors

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

Attenuation of tolerance to opioid‐induced antinociception and protection against morphine‐induced decrease of neurofilament proteins by idazoxan and other I2‐imidazoline ligands

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Attenuation of tolerance to opioid‐induced antinociception and protection against morphine‐induced decrease of neurofilament proteins by idazoxan and other I₂‐imidazoline ligands