Discriminative stimulus properties of the atypical antipsychotic amisulpride: comparison to its isomers and to other benzamide derivatives, antipsychotic, antidepressant, and antianxiety drugs in C57BL/6 mice

Donahue, Timothy J.; Hillhouse, Todd M.; Webster, Kevin A.; Young, Richard; Oliveira, Eliseu O. De; Porter, Joseph H.

doi:10.1007/s00213-017-4738-y

Cited by 8 publications

(8 citation statements)

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“…The present study replicated previous findings (Donahue et al ., 2017) that 10 mg/kg amisulpride has a robust discriminative stimulus being rapidly acquired in adult, male C57BL/6 mice, and provided information about the potential role of dopamine D 2/3 receptors, serotonin 5-HT 7 , and 5-HT 2B receptors in amisulpride’s discriminative stimulus properties. Amisulpride displayed a complex (or compound) discriminative cue that seems to involve (a) mixed antagonism/agonist at dopamine D 2/3 receptors), (b) some mixed agonist/antagonist effects at serotonin 5-HT 7 receptors, and (c) effects at 5-HT 2B receptors (Figs.…”

Section: Discussionsupporting

confidence: 93%

“…1) and benzamides that are predominately dopamine D 2/3 receptor antagonists (i.e. sulpride, ( S )-sulpride, and tiapride) produce full or high partial substitution for amisulpride (Donahue et al , 2017). Additionally, pretreatment with the dopamine D 2/3 receptor agonist quinpirole (0.32 mg/kg) prior to 10 mg/kg amisulpride in the present study markedly attenuated amisulpride-lever responding from 98.3% DLR to 57.0% DLR (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Training and testing sessions were conducted consistent with our previous amisulpride drug discrimination study (see Donahue et al , 2017 for detailed methods). Mice were placed in the operant chambers for 15-min sessions (usually 6 days per week) and initially trained on a fixed ratio (FR) 1 reinforcement schedule.…”

Section: Methodsmentioning

confidence: 99%

“…Test sessions generally occurred twice a week (typically Wednesdays and Saturdays). The doses for generalization testing (linear scale) were based on the doses from Donahue et al , (2017) in order to compare results with that study. After the mice completed the amisulpride generalization dose-effect curve, subsets of mice were used for substitution (N = 6) and combination (N = 8) testing to reduce drug history effects across mice.…”

Section: Methodsmentioning

confidence: 99%

“…The antipsychotic activity of racemic amisulpride (and other benzamides) is thought to depend on dopamine D 2/3 receptor activity, while its antidepressant activity is thought to depend on binding to serotonin 5-HT 7 receptors (Abbas et al ., 2009; Donahue et al ., 2017; Grattan et al ., 2019). Previously, we have shown that the discriminative stimulus properties of racemic amisulpride generalized to some, but not all benzamides.…”

Section: Introductionmentioning

confidence: 99%

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Examination of the mechanisms underlying the discriminative stimulus properties of the atypical antipsychotic amisulpride

Donahue,

Hillhouse,

Webster

et al. 2023

Behavioural Pharmacology

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Amisulpride is an atypical benzamide antipsychotic/antidepressant, whose mechanism of action is thought to depend mainly on dopamine D2/3 receptor activity, but also with some serotonin 5-HT2B/7 effects. The present study examined the role of D2/3 receptors and 5-HT2B/7 receptors in amisulpride’s discriminative stimulus. Selective agonists and antagonists of the above receptors were tested in adult, male C57BL/6 mice trained to discriminate 10 mg/kg amisulpride from vehicle in a two-lever drug discrimination assay. After acquisition of the two-lever discrimination, the amisulpride generalization curve yielded an ED50 = 0.56 mg/kg (95% CI = 0.42–0.76 mg/kg). Substitution tests found that the D2/3 antagonist raclopride (62.7% Drug Lever Responding), D2/3 agonist quinpirole (56.6% DLR), 5-HT7 agonist LP-44 (50.1% DLR) and 5-HT7 antagonist SB-269970 (36.7% DLR) produced various degrees of partial substitution for the amisulpride stimulus, whereas the 5-HT2B agonist BW 723C86 (17.9% DLR) and 5-HT2B antagonist SB-204741 (21.1% DLR) yielded negligible amisulpride-like effects. In combination tests with amisulpride, quinpirole decreased percent responding from 98.3% to 57.0% DLR, LP-44 decreased percent responding from 97.6% to 76.7% DLR, and BW 723C86 reduced percent responding from 95.66% to 74.11% DLR. Taken together, the results from stimulus generalization and antagonism studies suggest that amisulpride has a complex discriminative cue that involves mainly mixed D2/3 receptor antagonist/agonist effects and, to a lesser degree, mixed 5-HT7 receptor agonist/antagonist and perhaps 5-HT2B receptor antagonist effects.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Examination of the mechanisms underlying the discriminative stimulus properties of the atypical antipsychotic amisulpride

Donahue,

Hillhouse,

Webster

et al. 2023

Behavioural Pharmacology

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Drug Discrimination: Historical Origins, Important Concepts, and Principles

Porter

Prus

Overton

2018

Current Topics in Behavioral Neurosciences

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Research on the stimulus properties of drugs began with studies on state dependent learning during the first half of the twentieth century. From that research, an entirely new approach evolved called drug discrimination. Animals (including humans) could discriminate the presence or absence of a drug; once learned, the drug could serve as a discriminative stimulus, signaling the availability or nonavailability of reinforcement. Early drug discrimination research involved the use of a T-maze task, which evolved in the 1970s into a two-lever operant drug discrimination task that is still used today. A number of important concepts and principles of drug discrimination are discussed. (1) The discriminative stimulus properties of drugs are believed in large part to reflect the subjective effects of drugs. While it has been impossible to directly measure subjective effects in nonhuman animals, drug discrimination studies in human subjects have generally supported the belief that discriminative stimulus properties of drugs in nonhuman animals correlate highly with subjective effects of drugs in humans. In addition to the ability of the drug discrimination procedure to measure the subjective effects of drugs, it has a number of other strengths that help make it a valuable preclinical assay. (2) Drug discrimination can be used for classification of drugs based on shared discriminative stimulus properties. (3) The phenomena of tolerance and cross-tolerance can be studied with drug discrimination. (4) Discriminative stimulus properties of drugs typically have been found to be stereospecific, if a drug is comprised of enantiomers. (5) Discriminative stimulus properties of drugs reflect specific CNS activity at neurotransmitter receptors. (6) Both human and nonhuman subjects display individual differences in their sensitivity to discriminative stimuli and drugs. (7) The drug discrimination procedure has been used extensively as a preclinical assay in drug development. This chapter is the first in the volume The Behavioural Neuroscience of Drug Discrimination, which includes chapters concerning the discriminative stimulus properties of various classes of psychoactive drugs as well as sections on the applications and approaches for using this procedure.

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Antidepressant-like effect of a selenopropargylic benzamide in mice: involvement of the serotonergic system

et al. 2020

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Discriminative stimulus properties of the atypical antipsychotic amisulpride: comparison to its isomers and to other benzamide derivatives, antipsychotic, antidepressant, and antianxiety drugs in C57BL/6 mice

Cited by 8 publications

References 56 publications

Examination of the mechanisms underlying the discriminative stimulus properties of the atypical antipsychotic amisulpride

Examination of the mechanisms underlying the discriminative stimulus properties of the atypical antipsychotic amisulpride

Drug Discrimination: Historical Origins, Important Concepts, and Principles

Antidepressant-like effect of a selenopropargylic benzamide in mice: involvement of the serotonergic system

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