Interaction of mGlu2/3 agonism with clozapine and lurasidone to restore novel object recognition in subchronic phencyclidine-treated rats

Horiguchi, Masaaki; Huang, Mei; Meltzer, Herbert Y.

doi:10.1007/s00213-011-2251-2

Cited by 58 publications

(47 citation statements)

References 69 publications

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“…Our results confirm that subchronic PCP treatment (2 mg/kg i.p., twice a day for 7 days) induces a robust, persistent impairment in NOR (Grayson et al, 2007;Snigdha et al, 2010;Horiguchi et al, 2011). Our results provide additional support for the conclusion that this model is valuable for detecting compounds with therapeutic potential in treating CIS.…”

Section: Discussionsupporting

confidence: 76%

“…Atypical APDs (e.g., clozapine), but not the typical APD haloperidol, have been reported to reverse cognitive deficits induced by subchronic PCP treatment in NOR (Grayson et al, 2007;Snigdha et al, 2010). We recently reported that 5-HT 2A antagonists (e.g., pimavanserin) and the mGluR2/3 agonist LY379268 (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid), but not haloperidol, can potentiate the ability of subeffective doses of several atypical APDs, including lurasidone, to ameliorate the PCP-induced NOR deficit Horiguchi et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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The Role of 5-Hydroxytryptamine 7 Receptors in the Phencyclidine-Induced Novel Object Recognition Deficit in Rats

Horiguchi

Huang²,

Meltzer³

2011

J Pharmacol Exp Ther

120

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The role of 5-hydroxytryptamine (serotonin) (5-HT) 7 receptor antagonism in the actions of atypical antipsychotic drugs (APDs), e.g., amisulpride, clozapine, and lurasidone, if any, is uncertain. We examined the ability of 5-HT 7 receptor antagonism alone and as a component of amisulpride and lurasidone to reverse deficits in rat novel object recognition (NOR) produced by subchronic treatment with the N-methyl-D-aspartate receptor antagonist phencyclidine (PCP), and we examined the ability of supplemental 5-HT 7 antagonism to augment the inability of sulpiride, haloperidol, and (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY379268), a metabotropic glutamate receptor (mGluR) 2/3 agonist, which lack 5-HT 7 antagonism, to reverse the NOR deficit. The 5-HT 7 receptor antagonist, (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine (SB269970) (0.1-1 mg/kg) dose-dependently reversed PCP-induced NOR deficits. In addition, the ability of lurasidone (0.1 mg/kg) and amisulpride (3 mg/kg) to reverse this deficit was blocked by cotreatment with the 5-HT 7 receptor agonist (2S)-(ϩ)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin (AS19) (5-10 mg/kg), which did not affect NOR in naive rats. Sulpiride, a less potent 5-HT 7 antagonist than amisulpride, did not itself improve the PCPinduced NOR deficit. However, a subeffective dose of SB269970 (0.1 mg/kg) in combination with subeffective doses of lurasidone (0.03 mg/kg), amisulpride (1 mg/kg), or sulpiride (20 mg/kg), also reversed the PCP-induced NOR deficit. Pimavanserin, a 5-HT 2A inverse agonist, LY379268, and haloperidol did not potentiate the ability of subeffective SB269970 to improve the NOR deficit. Furthermore, the mGluR2/3 antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid (LY341495), which blocks the effect of clozapine to reverse the NOR deficit, did not block the SB269970-induced amelioration of the NOR deficit. These results suggest 5-HT 7 antagonism may contribute to the efficacy of some atypical APDs in the treatment of cognitive impairment in schizophrenia and may itself have some benefit in this regard.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

The Role of 5-Hydroxytryptamine 7 Receptors in the Phencyclidine-Induced Novel Object Recognition Deficit in Rats

Horiguchi

Huang²,

Meltzer³

2011

J Pharmacol Exp Ther

120

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“…mGlu2/3-receptor agonists have been reported not to improve either the NMDA-receptor antagonists-induced impairment of working memory (39) or the NMDAreceptor antagonist-induced impairment of object recognition (40), although mGlu2/3-receptor agonists improved object recognition impairment in rodents reared in social isolation or in mice lacking the pituitary adenylate cyclase-activating polypeptide (41 -43). Moreover, the stimulation of the mGlu2 receptor or the blockade of the mGlu1 receptor reportedly caused cognitive impairment itself (19,44,45).…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Metabotropic Glutamate (mGlu) 2 Receptor and Blockade of mGlu1 Receptor Improve Social Memory Impairment Elicited by MK-801 in Rats

et al. 2013

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Abstract. Glutamatergic dysfunction has been implicated in psychiatric disorders such as schizophrenia. Both the stimulation of the metabotropic glutamate (mGlu) 2/3 receptor and the blockade of the mGlu1 receptor have been shown to be effective in a number of animal models of schizophrenia. However, the efficacy for social cognition, which is poorly managed by current medication, has not been fully addressed. The present study evaluated the effects of an mGlu2/3-receptor agonist and an mGlu1-receptor antagonist on social memory impairment in rats. Pretreatment with an mGlu2/3-receptor agonist, (−)-2-oxa-4-aminobicyclo[3. propanoic acid (LY341495). These findings indicate that both the stimulation of the mGlu2 receptor and the inhibition of an mGlu1 receptor improve social memory impairment elicited by MK-801, and both manipulations could be effective approaches for the treatment of certain cognitive dysfunctions observed in schizophrenic patients.

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“…LY379268 improves object recognition following social isolation during adolescence [24] or acute MK-801 treatment in adulthood [36]. In combination with low doses of clozapine and lurasidone, LY379268 also reversed the disruptive effects of subchronic phencyclidine on object recognition [37]. Group II agonists also have inconsistent effects on the working memory impairments observed following administration phencyclidine [33,38].…”

Section: Discussionmentioning

confidence: 99%

Altered object exploration but not temporal order memory retrieval in an object recognition test following treatment of rats with the group II metabotropic glutamate receptor agonist LY379268

Lins¹,

Ballendine²,

Howland³

2014

Neuroscience Letters

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Temporal order memory refers to the ability to distinguish past experiences in the order that they occurred. Temporal order memory for objects is often tested in rodents using spontaneous object recognition paradigms. The circuitry mediating memory in these tests is distributed and involves ionotropic glutamate receptors in the perirhinal cortex and medial prefrontal cortex. It is unknown what role, if any, metabotropic glutamate receptors have in temporal order memory for objects. The present experiment examined the role of metabotropic glutamate receptors in temporal memory retrieval using the group II metabotropic glutamate receptor selective agonist LY379268. Rats were trained on a temporal memory test with three phases: two sample phases (60 min between them) in which rats explored two novel objects and a test phase (60 min after the second sample phase) which included a copy of each object previously encountered. Under these conditions, we confirmed that rats showed a significant exploratory preference for the object presented during the first sample phase. In a second experiment, we found that LY379268 (0.3, 1.0, or 3.0 mg/kg; i.p.; 30 min before the test phase) had no effect on temporal memory retrieval but dose-dependently reduced time spent exploring the objects. Our results show that enhancing mGluR2 activity under conditions when TM is intact does not influence memory retrieval.

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Interaction of mGlu2/3 agonism with clozapine and lurasidone to restore novel object recognition in subchronic phencyclidine-treated rats

Cited by 58 publications

References 69 publications

The Role of 5-Hydroxytryptamine 7 Receptors in the Phencyclidine-Induced Novel Object Recognition Deficit in Rats

The Role of 5-Hydroxytryptamine 7 Receptors in the Phencyclidine-Induced Novel Object Recognition Deficit in Rats

Stimulation of Metabotropic Glutamate (mGlu) 2 Receptor and Blockade of mGlu1 Receptor Improve Social Memory Impairment Elicited by MK-801 in Rats

Altered object exploration but not temporal order memory retrieval in an object recognition test following treatment of rats with the group II metabotropic glutamate receptor agonist LY379268

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