Effects of risperidone on locomotor activity and spatial memory in rats with hippocampal damage

Bardgett, Mark E.; Baum, Katherine T.; O'Connell, Shannon M.; Lee, Nathan M.; Hon, J

doi:10.1016/j.neuropharm.2006.07.014

Cited by 23 publications

(20 citation statements)

References 39 publications

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“…Rats were tested in the delayed spatial alternation task as previously described (Bardgett et al, 2006a & 2006b; 2008), using a 10 and 40 second delay between free and forced choice runs. As shown in Figure 4, MK-801 was found to decrease the number of correct choices at each delay in a dose-dependent manner (Treatment effect: F (2, 72) = 42.1 & 44.8, p < .0001 for the 10 and 40 second delays, respectively).…”

Section: Resultsmentioning

confidence: 99%

Effects of the H3 antagonist, thioperamide, on behavioral alterations induced by systemic MK-801 administration in rats

et al. 2009

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Rationale-Recent studies have raised the possibility that antagonists of H 3 histamine receptors possess cognitive-enhancing and antipsychotic properties. However, little work has assessed these compounds in classic animal models of schizophrenia.Objectives-The purpose of this study was to determine if a prototypical H 3 antagonist, thioperamide, could alter behavioral deficits caused by the NMDA receptor antagonist, MK-801, in adult male rats. MK-801 was chosen for study since it produces a state of NMDA receptor hypofunction in rats that may be analogous to the one hypothesized to occur in schizophrenia.Methods-The interaction between thioperamide and MK-801 was measured in three behavioral tests: locomotor activity, prepulse inhibition (PPI), and delayed spatial alternation. In each test, rats received a subcutaneous injection of saline or thioperamide (3.0 & 10 mg/kg) followed 20 minutes later by a subcutaneous injection of saline or MK-801 (0.05, 0.10, & 0.30 mg/kg).Results-Locomotor activity was significantly elevated by MK-801 in a dose-dependent manner. Thioperamide pretreatment alone did not alter locomotor activity, however its impact on MK-801 was dose-dependent. Each thioperamide dose enhanced the effects of two lower doses of MK801 but reduced the effect of a higher MK-801 dose. Clear deficits in PPI and delayed spatial alternation were produced by MK-801 treatment, but neither impairment was significantly modified by thioperamide pretreatment.Conclusions-H 3 receptors modulate responses to NMDA antagonists in behaviorally-specific ways and dependent upon the level of NMDA receptor blockade.

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Section: Resultsmentioning

confidence: 99%

Effects of the H3 antagonist, thioperamide, on behavioral alterations induced by systemic MK-801 administration in rats

et al. 2009

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“…The limitation to this claim is that H 3 antagonists may exacerbate other behavioral outcomes associated with such pathophysiology. At the very least, the data do not support the idea of H 3 antagonists as stand-alone antipsychotic drugs, although it still remains possible that H 3 antagonists may augment the cognitive-enhancing effects of antipsychotic drugs (Pillot et al, 2002b; Bardgett et al, 2006a; 2006b, Grayson et al, 2007) by modifying neurotransmitter release upstream of post-synaptic receptor sites occupied by such drugs. Additional research is needed to determine if H 3 antagonists can improve memory without perturbing the impact of pathophysiology on other behaviors associated with mental disorders or cognitive dysfunction.…”

Section: Discussionmentioning

confidence: 97%

The H3 antagonist, ciproxifan, alleviates the memory impairment but enhances the motor effects of MK-801 (dizocilpine) in rats

et al. 2010

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Summary Antagonists of H3-type histamine receptors exhibit cognitive-enhancing properties in various memory paradigms as well as evidence of antipsychotic activity in normal animals. The present study determined if a prototypical H3 antagonist, ciproxifan, could reverse the behavioral effects of MK-801, a drug used in animals to mimic the hypoglutamatergic state suspected to exist in schizophrenia. Four behaviors were chosen for study, locomotor activity, ataxia, prepulse inhibition (PPI), and delayed spatial alternation, since their modification by dizocilpine (MK-801) has been well characterized. Adult male Long-Evans rats were tested after receiving a subcutaneous injection of ciproxifan or vehicle followed twenty minutes later by a subcutaneous injection of MK-801 or vehicle. Three doses of MK-801 (0.05, 0.1, & 0.3 mg/kg) increased locomotor activity. Each dose of ciproxifan (1.0 & 3.0 mg/kg) enhanced the effect of the moderate dose of MK-801, but suppressed the effect of the high dose. Ciproxifan (3.0 mg/kg) enhanced the effects of MK-801 (0.1 & 0.3 mg/kg) on fine movements and ataxia. Deficits in PPI were observed after treatment with MK-801 (0.05 & 0.1 mg/kg), but ciproxifan did not alter these effects. Delayed spatial alternation was significantly impaired by MK-801 (0.1 mg/kg) at a longer delay, and ciproxifan (3.0 mg/kg) alleviated this impairment. These results indicate that some H3 antagonists can alleviate the impact of NMDA receptor hypofunction on some forms of memory, but may exacerbate its effect on other behaviors.

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“…We also found that young rats between PNDs 14 and 42 were just as sensitive to the suppressive action of risperidone. Admittedly, the doses used here were higher than those typically administered to adult rats in order to characterize the more nuanced effects of risperidone on locomotor activity (Arnt, 1995; Bardgett et al, 2006). However, the selected doses were chosen based on their clinical relevance (Kapur et al, 2003) and their consistency with recent work on the behavioral and biochemical effects of early-life risperidone (Moran-Gates et al, 2007; Choi et al, 2009; 2010; Bardgett et al, 2013; Gannon et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Delayed yet persistent effects of daily risperidone on activity in developing rats

Stevens

Gannon²,

Griffith³

et al. 2016

Behavioural Pharmacology

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Early-life administration of risperidone, the most widely used antipsychotic drug in children, leads to persistently elevated locomotor activity in adult rats. This study determined if and when elevated locomotor activity emerges during developmental risperidone administration. Developing and adult rats were given daily injections of risperidone (1.0 and 3.0 mg/kg) or vehicle for four weeks beginning at postnatal day (PND) 14 and 74, respectively. Starting with the first injection and every seven days thereafter, locomotor activity was measured immediately after the injection and 20 minutes prior to the next day’s injection. Activity was also recorded one week after the final injection. Risperidone profoundly decreased locomotor activity in developing and adult rats immediately after injection. Within 24 h after their first injection, adult rats administered risperidone demonstrated greater activity levels. In contrast, developing rats did not demonstrate compensatory hyperactivity until the beginning of the fourth week of risperidone administration. One week after the final risperidone injection, there was no evidence of hyperactivity in the adult rats maintained on risperidone, but developing rats administered risperidone, especially females, exhibited greater activity levels relative to vehicle-administered controls. In comparison to adult rats, the emergence of compensatory hyperactivity during long-term APD administration is delayed in developing rats but persists after treatment cessation.

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Effects of risperidone on locomotor activity and spatial memory in rats with hippocampal damage

Cited by 23 publications

References 39 publications

Effects of the H3 antagonist, thioperamide, on behavioral alterations induced by systemic MK-801 administration in rats

Effects of the H3 antagonist, thioperamide, on behavioral alterations induced by systemic MK-801 administration in rats

The H3 antagonist, ciproxifan, alleviates the memory impairment but enhances the motor effects of MK-801 (dizocilpine) in rats

Delayed yet persistent effects of daily risperidone on activity in developing rats

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