N-methyl-d-aspartate produces discriminative stimuli in rats

Amrick, Caryl L.; Bennett, Debra A.

doi:10.1016/0024-3205(87)90373-0

Cited by 16 publications

(3 citation statements)

References 16 publications

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“…However, in another study using the elevated plus-maze 8-OH-DPAT produced an anxiogenic-like response (Critchley & Handley 1986a); the reason for this discrepancy is unclear. Conflict studies have reported both inactivity (Boast et a1 1983;Deacon & Gardener 1986) and anti-conflict activity (Engel et a1 1984;Amrick & Bennett 1986). Quantitative differences in behavioural responses to this drug have previously been reported between rat strains (Gudelsky et a1 1985).…”

Section: Discussionmentioning

confidence: 92%

“…There has been evidence for anxiolytic activity in a clinical trial (Ceulemans et a1 1985), in a light : dark crossing test (Colpaert et a1 1985) in rats and in another study using the elevated plus-maze (Critchley & Handley 1986b); however, other investigations using conflict tests have reported no activity or activity at only one dose (Colpaert et a1 1985;Amrick & Bennett 1986) and ritanserin gave no evidence for an anxiolytic profile in a social interaction test (Gardener 1986). There has been evidence for anxiolytic activity in a clinical trial (Ceulemans et a1 1985), in a light : dark crossing test (Colpaert et a1 1985) in rats and in another study using the elevated plus-maze (Critchley & Handley 1986b); however, other investigations using conflict tests have reported no activity or activity at only one dose (Colpaert et a1 1985;Amrick & Bennett 1986) and ritanserin gave no evidence for an anxiolytic profile in a social interaction test (Gardener 1986).…”

Section: Discussionmentioning

confidence: 99%

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Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat

Pellow

Johnston

File

1987

Journal of Pharmacy and Pharmacology

154

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The effects of some 5-HT receptor ligands were investigated on measures of anxiety in an elevated plus-maze test in the rat. Quipazine (2 and 4 mg kg-1), a non-specific 5-HT agonist and ritanserin (0.25-10 mg kg-1), a 5-HT2 receptor antagonist displayed anxiogenic profiles by reducing both of the measures of anxiety used in this test. Two 5-HT1A receptor ligands, buspirone (4 and 8 mg kg-1) and ipsapirone (2.5-10 mg kg-1) and the 5-HT1 agonist, RU 24969 (0.1875-1.5 mg kg-1) significantly reduced only the percentage of time spent on the open arms. (-)-Propranolol (5 and 10 mg kg-1), a 5-HT1 receptor antagonist significantly reduced only the percentage of entries made onto the open arms. Metergoline (4 mg kg-1), a non-specific 5-HT antagonist displayed anxiolytic effects in this test by increasing both measures of anxiety. The 5-HT1A receptor agonist, 8-OH-DPAT (0.0625-0.25 mg kg-1) had no effect on either of the measures of anxiety. The results from the non-specific ligands (quipazine and metergoline) are consistent with the theory that a reduction in 5-HT function reduces anxiety. However, in spite of their more selective effects on 5-HT receptors the results in this test from the more specific ligands are not consistent with a strong involvement of any single receptor subtype. The interaction studies with yohimbine and FG 7142 (beta-carboline-3-carboxylate methylamide) provided no clear evidence for a major role of 5-HT pathways in the mediation of their anxiogenic effects.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat

Pellow

Johnston

File

1987

Journal of Pharmacy and Pharmacology

154

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“…LY235959 (3 mg/kg) was administered subcutaneously 30 min prior to the start of self-administration sessions, and NMDA was administered intraperitoneally 10 or 30 min before the start of self-administration sessions. The doses of NMDA used in this study were chosen after reviewing the literature on NMDA discriminative stimulus effects in Sprague-Dawley rats (Amrick and Bennett, 1987;Grech et al, 1995). The effects of 100 mg/kg NMDA alone were not measured to avoid convulsions that could emerge with the systemic administration of this dose of NMDA alone (Giménez-Llort et al, 1995).…”

Section: Methodsmentioning

confidence: 99%

Effects of the Competitive N-Methyl-d-aspartate Receptor Antagonist, LY235959 [(-)-6-Phosphonomethyl-deca-hydroisoquinoline-3-carboxylic Acid], on Responding for Cocaine under Both Fixed and Progressive Ratio Schedules of Reinforcement

Allen¹,

Carelli²,

Dykstra³

et al. 2005

J Pharmacol Exp Ther

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It is difficult to determine the precise role of the N-methyl-Daspartate (NMDA) receptor system in the reinforcing effects of cocaine since uncompetitive NMDA receptor antagonists alter cocaine self-administration in different ways, depending on the antagonist examined and the behavior being measured. To increase understanding of the role of the NMDA system in cocaine's reinforcing effects, this study measured the effects of the competitive NMDA receptor antagonist, LY235959 [(Ϫ)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid], in rats that self-administered cocaine under both fixed ratio (FR) 1 and progressive ratio (PR) schedules of reinforcement. Rats were trained to self-administer cocaine (0.33 mg/infusion) under an FR1 schedule of reinforcement. Thereafter, the effects of pretreatment with LY235959, or the uncompetitive antagonists dextromethorphan and dizocilpine, were examined. The number of infusions earned during the first 10 min of responding under the FR1 schedule was analyzed separately. When rats responded for 0.33 mg/infusion cocaine under an FR1 schedule of reinforcement, 3 mg/kg LY235959 decreased cocaine selfadministration only during the first 10 min of the responding. This effect was dose and time dependent and blocked by the competitive NMDA receptor agonist, NMDA. LY235959 (3 mg/ kg) decreased total responding for cocaine only when the selfadministered dose of cocaine was small (0.02-0.04 mg/infusion) or when responding was reinforced under the PR schedule. In contrast, dizocilpine decreased responding under the FR1 schedule but increased responding under the PR schedule. These data suggest that LY235959 decreased the reinforcing effectiveness of cocaine, a finding reported with systemically administered NMDA receptor antagonists other than dizocilpine.Data from animal studies show that self-administration of the psychomotor stimulant cocaine requires an intact mesolimbic dopamine system (Roberts and Koob, 1980;Pettit et al., 1984;Caine and Koob, 1994). In addition to the primary dopaminergic projection from the ventral tegmental area to the nucleus accumbens, the mesolimbic system receives extensive innervations from glutamatergic efferent projections originating in various cortical and subcortical structures, including the prefrontal cortex, hippocampus, and basolateral amygdala (for review, see Baker et al., 2002). Recent demonstrations that some forms of long-term potentiation are dependent upon the N-methyl-D-aspartate (NMDA) glutamate receptor system in the nucleus accumbens (Kombian and Malenka, 1994;Thomas et al., 2000) and ventral teg-

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Drug Discrimination: Practical Considerations

2011

Drug Discrimination

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N-methyl-d-aspartate produces discriminative stimuli in rats

Cited by 16 publications

References 16 publications

Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat

Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat

Effects of the Competitive N-Methyl-d-aspartate Receptor Antagonist, LY235959 [(-)-6-Phosphonomethyl-deca-hydroisoquinoline-3-carboxylic Acid], on Responding for Cocaine under Both Fixed and Progressive Ratio Schedules of Reinforcement

Drug Discrimination: Practical Considerations

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