Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

McLean, Samantha L.; Woolley, Marie L.; Thomas, D R; Neill, Joanna C.

doi:10.1007/s00213-009-1618-0

Cited by 62 publications

(54 citation statements)

References 90 publications

(96 reference statements)

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“…This is a robust and long-lasting (up to 6 months post-PCP treatment, Idris, personal communication) effect continually produced by our laboratory (Abdul-Monim et al, 2006;Idris et al 2009;McLean et al, 2009a;2009b) and is also in agreement with results from other laboratories (Jentsch and Taylor, 2001). Sub-chronic PCP treatment did not affect total lever pressing, suggesting that neither locomotor activity nor motivation were affected, thus the apparent cognitive deficits in the reversal phase were not due to any other effects of PCP.…”

Section: Discussionsupporting

confidence: 88%

“…For a recent review of the involvement of α7 nACh receptors in cognitive processing of relevance to schizophrenia, see Leiser et al 2009. Our laboratory aims to model, in rats, the seven domains of cognition highlighted by the MATRICS initiative as being impaired in schizophrenia patients (Green et al, 2004;Marder and Fenton, 2004). In our hands, this has predominantly involved the implementation of an operant reversal learning task (Abdul-Monim et al, 2003;2006;Idris et al, 2005;McLean et al, 2009a;2009b), the attentional setshifting task (McLean et al, 2008; and the ethologically relevant, novel object recognition task (Grayson et al, 2007;Idris et al, 2009;McLean et al, 2009a). We have repeatedly demonstrated that a sub-chronic PCP dosage regimen produces robust deficits in these behavioural tests (for review see Neill et al, 2010); and that these deficits are accompanied by reductions in parvalbumin-immunoreactive neurons in the hippocampus and M1 (motor area 1) region of the frontal cortex (Abdul-Monim et al, 2007) and brain-derived neurotrophic factor (BDNF) levels in several cortical regions (Snigdha et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Activation of α7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: Implications for therapy of cognitive dysfunction in schizophrenia

McLean

Grayson

Idris

et al. 2011

European Neuropsychopharmacology

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Rationale: Nicotinic α7 acetylcholine receptors (nAChRs) have been highlighted as a target for cognitive enhancement in schizophrenia. Aim: To investigate whether the deficits induced by sub-chronic phencyclidine (PCP) in reversal learning and novel object recognition could be attenuated by the selective α7 nAChR full agonist, PNU-282987. Methods: Adult female hooded-Lister rats received sub-chronic PCP (2 mg/kg) or vehicle i.p. twice daily for seven days, followed by 7-days washout. In cohort 1, PCP-treated rats then received PNU-282987 (5, 10, 20 mg/kg; s.c.) or vehicle and were tested in the reversal learning task. In cohort 2, PCP-treated rats received PNU-282987 (10 mg/kg; s.c.) or saline for 15 days and were tested in the novel object recognition test on day 1 and on day 15, to test for tolerance. Results: Sub-chronic PCP produced significant deficits in both cognitive tasks (P<0.01-0.001).PNU-282987 attenuated the PCP-induced deficits in reversal learning at 10 mg/kg (P<0.01) and 20 mg/kg (P<0.001), and in novel object recognition at 10 mg/kg on day 1 (P<0.01) and on day 15 (P<0.001). Conclusions: These data show that PNU-282987 has efficacy to reverse PCP-induced deficits in two paradigms of relevance to schizophrenia. Results further suggest that 15 day daily dosing of PNU-282987 (10 mg/kg s.c.) does not cause tolerance in rat. This study suggests that activation of α7 nAChRs, may represent a suitable strategy for improving cognitive deficits of relevance to schizophrenia.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Activation of α7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: Implications for therapy of cognitive dysfunction in schizophrenia

McLean

Grayson

Idris

et al. 2011

European Neuropsychopharmacology

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“…Thus, SB269970 improved reference memory in a radial arm maze (Gasbarri et al, 2008) and a PCPinduced reversal learning deficit in rats (McLean et al, 2009). Consistent with these reports, several studies have demonstrated a procognitive effect of 5-HT 7 antagonists (see Discussion).…”

Section: Introductionsupporting

confidence: 78%

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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“…We have consistently shown that sub-chronic PCP treatment (2 mg/kg twice daily, i.p., for 7 days followed by 7 days washout period) induces a robust enduring deficit in reversal learning performance, again selective for the reversal phase leaving initial phase performance intact in female hooded-Lister rats (Abdul-Monim et al, 2006;2007;Idris et al 2010;McLean et al, 2009a;2009b). …”

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confidence: 99%

“…Several newer antipsychotics such as asenapine (M c Lean et al 2010b) and sertindole (Idris et al, 2010) reverse the sub-chronic PCP-induced deficit in this paradigm. The dopamine D 1 receptor agonist SKF 38393 and antagonists at several 5-HT receptor subtypes including 5-HT 6 , 5-HT 7 , 5-HT 2C and 5-HT 2A (Idris et al 2010;McLean et al, 2009a;2009b) also show efficacy in this test making it of particular relevance for exploration of mechanisms of antipsychotics important for improvement of cognitive function. In a reversal-learning task similar to that employed in our laboratory, however, using an innovative touch screen-based system, sub-chronic PCP (5 mg/kg twice daily for 7 days, followed by a 7-day washout period) in male C57BL/6J mice did not affect reversal learning ability (Brigman et al, 2009).…”

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confidence: 99%

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Neill

Barnes

Cook

et al. 2010

Pharmacology & Therapeutics

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477

322

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Cognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro-and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive disturbances of relevance to schizophrenia in rodents and their subsequent reversal by first-and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-choice serial reaction time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel therapies for improved therapy of cognitive deficits and negative symptoms in schizophrenia.

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Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

Cited by 62 publications

References 90 publications

Activation of α7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: Implications for therapy of cognitive dysfunction in schizophrenia

Activation of α7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: Implications for therapy of cognitive dysfunction in schizophrenia

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

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

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