Competitive and noncompetitive NMDA antagonists block sensitization to methamphetamine

doi:10.1016/0091-3057(94)90318-2

Pharmacology Biochemistry and Behavior

Volume 48, Issue 3, July 1994, Pages 587-591

https://doi.org/10.1016/0091-3057(94)90318-2 Get rights and content

Abstract

The present study examined the effects of both competitive (D-CPP-ene) and noncompetitive (MK-801) NMDA antagonists on behavioral sensitization to methamphetamine (MA). Behavioral effects of repeated administration of NMDA antagonists were also examined. Rats treated with MA according to an escalating dose schedule (2.5, 5, 7.5, and 10.0 mg/kg, SC, twice a day on days 1, 3, 5, and 7, respectively) indicated behavioral supersensitivity. Pretreatment with either MK-801 (0.5 mg/kg, IP) or D-CPP-ene (20 mg/kg, IP) prior to MA administration prevented the development of the supersensitivity. Rats treated with MK-801 showed a decrease in the motor activity when subsequently challenged with MK-801 compared with saline-treated rats. Likewise, rats administered with D-CPP-ene showed decreased motor activity when challenged with D-CPP-ene. There was no cross-sensitization nor tolerance between MA and MK-801 or D-CPP-ene. These results suggest that both competitive and noncompetitive NMDA antagonists block sensitization to MA and that repeated administration with NMDA antagonists results in behavioral tolerance.

References (38)

S. Castellani et al.
Acute and chronic phencyclidine effects on locomotor activity, stereotypy and ataxia in rats
Eur. J. Pharmacol.
(1981)
G.C. Collingridge et al.
Excitatory amino acid receptors and synaptic plasticity
Trends Pharmacol. Sci.
(1990)
H.E. Criswell et al.
Long-term D₁-dopamine receptor sensitization in neonatal 6-OHDA-lesioned rats is blocked by an NMDA antagonist
Brain Res.
(1990)
P.S. D'Aquila et al.
The NMDA receptor antagonist MK-801 prevents imipramine-induced supersensitivity to quinpirole
Eur. J. Pharmacol.
(1992)
M.G. De Montis et al.
NMDA receptor inhibition prevents tolerance to cocaine
Pharmacol. Biochem. Behav.
(1992)
P.W. Kalivas et al.
Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity
Brain Res. Rev.
(1991)
R. Karler et al.
Blockade of ‘reverse tolerance’ to cocaine and amphetamine by MK-801
Life Sci.
(1989)
R. Karler et al.
Amphetamine sensitization and the excitatory amino acids
Brain Res.
(1990)
J.M. Khanna et al.
Effect of NMDA receptor antagonists on rapid tolerance to ethanol
Eur. J. Pharmacol.
(1993)
M.T. Lowy
MK-801 antagonizes methamphetamine-induced decreases in hippocampal and striatal corticosteroid receptors
Brain Res.
(1990)

H.S. Lustig et al.

Antiparkinsonian drugs and in vitro excitotoxicity

Brain Res.

(1992)

A. Muraki et al.

MK-801, a noncompetitive antagonist of NMDA receptor, prevents methamphetamine-induced decrease of striatal dopamine uptake sites in the rat striatum

Neurosci. Lett.

(1992)

T. Nabeshima et al.

Development of tolerance and supersensitivity to phencyclidine in rats after repeated administration of phencyclidine

Eur. J. Pharmacol.

(1987)

M. Nakayama et al.

Long-lasting decrease in dopamine uptake sites following repeated administration of methamphetamine in the rat striatum

Brain Res.

(1993)

T. Ohmori et al.

Effect of phencyclidine on spontaneous and $N- methyl- D -aspartate$ (NKDA)-induced efflux of dopamine from superfused slices of rat striatum

Neuropharmacology

(1992)

T.E. Robinson et al.

Enduring changes in brain and behavior produced by chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosis

Brain Res. Rev.

(1986)

R.C. Smith et al.

Effects of chronic administration of phencyclidine on stereotyped and ataxic behaviors in the rat

Life Sci.

(1981)

L.D. Snell et al.

Comparison of the effects of MK-801 and phencyclidine on catecholamine uptate and NMDA-induced norepinephrine release

Eur. J. Pharmacol.

(1988)

F.B. Weihmuller et al.

MK-901 attenuates the dopamine-releasing but not the behavioral effects of methamphetamine: An in vivo microdialysis study

Brain Res.

(1991)

Cited by (102)

Enhanced methamphetamine sensitisation in a rat model of the brain-derived neurotrophic factor Val66Met variant: Sex differences and dopamine receptor gene expression
2023, Neuropharmacology
Brain-derived neurotrophic factor (BDNF) and the Val66Met polymorphism may play a role in the development of psychosis and schizophrenia. The aim of this study was to investigate long-term effects of methamphetamine (Meth) on psychosis-like behaviour and dopamine receptor and dopamine transporter gene expression in a novel rat model of the BDNF Val66Met polymorphism. At the end of a 7-day subchronic Meth treatment, female rats with the Met/Met genotype selectively showed locomotor hyperactivity sensitisation to the acute effect of Meth. Male rats showed tolerance to Meth irrespective of Val66Met genotype. Two weeks later, female Met/Met rats showed increased locomotor activity following both saline treatment or a low dose of Meth, a hyperactivity which was not observed in other genotypes or in males. Baseline PPI did not differ between the groups but the disruption of PPI by acute treatment with apomorphine was absent in Meth-pretreated Met/Met rats. Female Met/Met rats selectively showed down-regulation of dopamine D2 receptor gene expression in striatum. Behavioural effects of MK-801 or its locomotor sensitisation by prior Meth pretreatment were not influenced by genotype. These data suggest a selective vulnerability of female Met/Met rats to short-term and long-term effects of Meth, which could model increased vulnerability to psychosis development associated with the BDNF Val66Met polymorphism.
Ifenprodil attenuates the acquisition and expression of methamphetamine-induced behavioral sensitization and activation of Ras-ERK1/2 cascade in the caudate putamen
2016, Neuroscience
Chronic discontinuous use of many psychomotor stimulants leads to behavioral sensitization and, owing to it shares common mechanisms with relapse, most researchers use its animal model to explore the neurobiological mechanisms of addiction. Recent studies have proved that N-methyl-d-aspartate receptors (NMDARs) are implicated in psychomotor stimulant-induced behavioral sensitization. However, the function of GluN2B-containing NMDARs and their potential downstream cascade(s) in the acquisition and expression of behavioral sensitization to methamphetamine (METH) have not been explored. In this study, 2.5, 5, and 10 mg/kg ifenprodil, the specific inhibitor of GluN2B, was used to explore the function of these receptors in distinct phases of behavioral sensitization to METH in mice. Then, using western blot, Ras, pERK1/2/ERK1/2, and ΔFosB levels in the prefrontal cortex (PFc), nucleus accumbens (NAc), and caudate putamen (CPu) were detected. Behavioral results showed that low-dose ifenprodil attenuated the acquisition and expression of behavioral sensitization to METH significantly. Western blot analysis revealed that pre-injection of low-dose ifenprodil in the acquisition markedly attenuated METH-induced ascent of Ras, pERK1/2/ERK1/2, and ΔFosB protein levels in the CPu. However, pre-treatment in the expression only affected the alterations of Ras and pERK1/2/ERK1/2 levels in the CPu. Moreover, chronic METH administration increased pERK1/2/ERK1/2 level in the NAc. In conclusion, GluN2B-containing NMDARs contribute to both the acquisition and expression of behavioral sensitization to METH in mice. Furthermore, the acquisition phase might be mediated by the Ras-ERK1/2-ΔFosB cascade in the CPu while the expression phase may be regulated by the Ras-ERK1/2 cascade in the CPu.
Mirtazapine exerts an anxiolytic-like effect through activation of the median raphe nucleus-dorsal hippocampal 5-HT pathway in contextual fear conditioning in rats
2016, Progress in Neuro-Psychopharmacology and Biological Psychiatry
Citation Excerpt :
Immediately after testing the expression of conditioned fear, rats were individually placed in a testing cage (38 × 33 × 17 cm) for the evaluation of spontaneous activity. Motor activity was automatically recorded, as described previously (Ohmori et al., 1994), using an apparatus with an infrared sensor that detects thermal radiation from animals over a period of 10 min (Supermex; Muromachi, Japan). Horizontal movement was digitized and used as the measure of general motor activity.
The functional role of serotonergic projections from the median raphe nucleus (MRN) to the dorsal hippocampus (DH) in anxiety remains understood poorly. The purpose of the present research was to examine the functional role of this pathway, using the contextual fear conditioning (CFC) model of anxiety. We show that intra-MRN microinjection of mirtazapine, a noradrenergic and specific serotonergic antidepressant, reduced freezing in CFC without affecting general motor activity dose-dependently, suggesting an anxiolytic-like effect. In addition, intra-MRN microinjection of mirtazapine dose-dependently increased extracellular concentrations of serotonin (5-HT) but not dopamine in the DH. Importantly, intra-DH pre-microinjection of WAY-100635, a 5-HT_1A antagonist, significantly attenuated the effect of mirtazapine on freezing. These results, for the first time, suggest that activation of the MRN-DH 5-HT_1A pathway exerts an anxiolytic-like effect in CFC. This is consistent with the literature that the hippocampus is essential for retrieval of contextual memory and that 5-HT_1A receptor activation in the hippocampus primarily exerts an inhibitory effect on the neuronal activity.
Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects
2016, Progress in Molecular Biology and Translational Science
Addiction to psychostimulants has been considered as a chronic psychiatric disorder characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that result in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction.
Memantine prevents "bipolar-like" behavior induced by chronic treatment with imipramine in rats
2015, European Journal of Pharmacology
Citation Excerpt :
Indeed, although the exact molecular mechanisms underlying the behavioral sensitization remain to be clarified (Ujike et al., 2002a; 2002b; Kawasaki et al., 2004; Landa et al., 2014), there is ample experimental evidence showing that the NMDA glutamate receptor plays an essential role in sensitization phenomena, especially in the sensitization (or reverse tolerance) to psychostimulants (Landa et al., 2014) that results in manic-like behaviors in animals and humans. Its stimulation is, in fact, necessary for the sensitization of amphetamine (Wolf et al., 1994; Ohmori et al., 1994; Vezina and Queen, 2000; Battisti et al., 2000; Pacchioni et al., 2002; Grönig et al., 2004), methylphenidate (Gaytan et al., 2000), cocaine (Li et al., 2000; Heusner and Palmiter, 2005; Rompré et al., 2006; Kim et al., 1996), apomorphine (Võikar et al., 1999; Acerbo et al., 2004) and other dopamine mimetics (Kalivas, 1995; Rockhold, 1998), nicotine (Kelsey et al., 2002), morphine (Jeziorski et al., 1994; Trujillo, 2002) and ethanol (Broadbent and Weitemier, 1999; Camarini et al., 2000; Kotlinska et al., 2006), as well as several types of stress such as, for instance, ‘restraint stress’ (Pacchioni et al., 2002) and ‘social defeat stress’ (Yap et al., 2005). Incidentally, it is worth recalling that the sensitization (also called reverse tolerance) to psychostimulants (amphetamine-cocaine) results in manic-like behaviors in animals and in manic-like syndromes in humans (indeed, the so called “ amphetamine psychosis” considered for a long time as “paranoid schizophrenia”, can be considered, in accordance with the more recent nosography, a manic episode with psychotic symptoms).
A great deal of evidence suggests that virtually all antidepressant treatments induce a dopaminergic behavioral supersensitivity. We have suggested that this effect may play a key role not only in the antidepressant effect of these treatments, but also in their ability to induce a switch from depression to mania. In 2003-4 we found that the sensitization of dopamine receptors induced by imipramine is followed, after imipramine withdrawal, by a desensitization of these receptors associated with a depressive-like behavior assessed in the forced swimming test. The dopamine receptor sensitization can be prevented by MK-801, an NMDA receptor antagonist, but not by currently used mood stabilizers (lithium, carbamazepine, valproate). These observations led us to suggest – and later confirm - with preliminary clinical observations that memantine may have an acute antimanic and a long-lasting mood-stabilizing effect in treatment-resistant bipolar disorder patients. Here we present data showing that memantine prevents not only the dopamine receptor sensitization induced by imipramine, as observed with MK-801, but also the ensuing desensitization and the associated depressive-like behaviorq observed after antidepressant withdrawal.
Subchronic lithium treatment increases the anxiolytic-like effect of mirtazapine on the expression of contextual conditioned fear
2015, European Journal of Pharmacology
Lithium not only has a mood-stabilizing effect but also the augmentation effect of an antidepressant, the mechanism of which remains unclear. Although lithium may augment the effect of mirtazapine, this augmentation has not been confirmed. Using a contextual fear conditioning test in rats, an animal model of anxiety or fear, we examined the effect of subchronic lithium carbonate (in diet) in combination with systemic mirtazapine on the expression of contextual conditioned fear. Mirtazapine (10 mg/kg) reduced freezing one day after fear conditioning dose-dependently, whereas the anxiolytic-like effect of mirtazapine (10 mg/kg) diminished seven days after fear conditioning. When the interval between fear conditioning and testing was seven days, only the combination of subchronic 0.2% Li₂CO₃ but not 0.05% Li₂CO₃ with acute mirtazapine (10 mg/kg) reduced freezing significantly. These results indicate that subchronic 0.2% Li₂CO₃ treatment enhanced the anxiolytic-like effect of systemic mirtazapine. This augmentation therapy might be useful for the treatment of anxiety disorders.

View all citing articles on Scopus

View full text

Competitive and noncompetitive NMDA antagonists block sensitization to methamphetamine

Abstract

Eur. J. Pharmacol.

Trends Pharmacol. Sci.

Brain Res.

Eur. J. Pharmacol.

Pharmacol. Biochem. Behav.

Brain Res. Rev.

Life Sci.

Brain Res.

Eur. J. Pharmacol.

Brain Res.

Brain Res.

Neurosci. Lett.

Eur. J. Pharmacol.

Brain Res.

Neuropharmacology

Brain Res. Rev.

Life Sci.

Eur. J. Pharmacol.

Brain Res.