Investigation of the effects of lamotrigine and clozapine in improving reversal-learning impairments induced by acute phencyclidine and d-amphetamine in the rat

Abstract

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Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats

“…Reversal learning has been studied as a measure of cognitive flexibility in humans (Fellows and Farah 2003;Murphy et al 2002;Rogers et al 2000;Rolls et al 1994), nonhuman primates (Clarke et al 2004;Clarke et al 2005;Clarke et al 2007;Dias et al 1996;Lee et al 2007), and rats (Birrell and Brown 2000;Boulougouris et al 2007a;Boulougouris et al 2007b;Idris et al 2005;McAlonan and Brown 2003;van der Meulen et al 2007). Effective reversal learning involves a number of specific and distinct operations, including: 1) detection of the shift in contingency (i.e., "error detection"); 2) inhibition of the prepotent, previously learned positive response; 3) overcoming learned avoidance of the previously negative stimulus; and 4) acquisition of the new association.…”

A preliminary investigation into the effects of antipsychotics on sub-chronic phencyclidine-induced deficits in attentional set-shifting in female rats

“…The doses of clozapine and risperidone were chosen on the basis of our previous work showing efficacy against sub-chronic PCP-induced deficits in reversal learning [2,42] and NOR [22]. The dose of haloperidol was chosen on the basis of our previous work showing that 0.05 mg/kg haloperidol significantly attenuated a d-amphetamine-induced reversal learning impairment in female hooded-Lister rats [28]. We believe a higher dose of haloperidol would not have been any more effective as a dose of 0.075 mg/kg haloperidol was less efficacious to reverse the amphetamine deficit in reversal learning when compared to the dose of 0.05 mg/kg [28] and a dose of 0.1 mg/kg was shown to impair performance [1].…”

“…The dose of haloperidol was chosen on the basis of our previous work showing that 0.05 mg/kg haloperidol significantly attenuated a d-amphetamine-induced reversal learning impairment in female hooded-Lister rats [28]. We believe a higher dose of haloperidol would not have been any more effective as a dose of 0.075 mg/kg haloperidol was less efficacious to reverse the amphetamine deficit in reversal learning when compared to the dose of 0.05 mg/kg [28] and a dose of 0.1 mg/kg was shown to impair performance [1]. Furthermore 0.05 mg/kg haloperidol has been shown to occupy 50% of dopamine D 2 receptors [34,35].…”

“…The dose of haloperidol was chosen on the basis of a previous study showing that 0.05 mg/kg haloperidol significantly attenuated a d-amphetamine-induced reversal learning impairment in female hooded-Lister rats [28]. Furthermore, this dose of haloperidol has been shown to occupy 50% of dopamine D 2 receptors [34,35].…”

“…This disinhibition of excitatory neurotransmission is referred to as NMDA receptor hypofunction [32,45,46]. Acute administration of PCP in rats has been shown to produce deficits in the novel object recognition-NOR-task [21], an operant reversal learning paradigm [1,28] and attentional set-shifting [16].…”