Differential effects of neuroleptic and other psychotropic agents on acquisition of avoidance in rats

Davidson, Arnold B.; Weidley, E. F.

doi:10.1016/0024-3205(76)90205-8

Cited by 83 publications

(33 citation statements)

References 7 publications

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“…The behavioral studies using rats, antagonism of dopamine agonist-induced hyperlocomotion (Janssen et al, 1965;Ogren et al, 1984;Gustafsson and Christensson, 1990;Moore and Kenyon, 1994) and conditioned avoidance response (CAR) paradigm (Cook et al, 1955;Davidson and Weidley, 1976;Arnt, 1982; for review, see Wadenberg et al, 1999) have traditionally been used to predict the antipsychotic efficacy of novel agent. In the present study, YKP1447 dose-dependently inhibited d-amphetamine-induced hyperlocomotion activity in rats, indicating the antipsychotic action of YKP1447.…”

Section: Discussionmentioning

confidence: 99%

YKP1447, A Novel Potential Atypical Antipsychotic Agent

Dong

Heo

et al. 2009

Korean J Physiol Pharmacol

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(S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-HT2A, Ki=0.61 nM, 5-HT2C, Ki=20.7 nM) and dopamine (D2, Ki=45.9 nM, D3, Ki=42.1 nM) receptors with over 10∼ 100-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing (ED50=0.93 mg/kg) and DOI-induced head twitch (ED50=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine (ED50=0.54 mg/kg) and the avoidance response (ED50=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose (ED50=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.

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Section: Discussionmentioning

confidence: 99%

YKP1447, A Novel Potential Atypical Antipsychotic Agent

Dong

Heo

et al. 2009

Korean J Physiol Pharmacol

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“…It is well established that low (noncataleptic) doses of all APDs, administered after the avoidance behavior has been acquired, selectively disrupt that avoidance response yet leave the escape response intact (Ader & Clink, 1957;Arnt, 1982;Cook & Weidley, 1957;Cook & Catania, 1964;Courvoisier, 1956b;Davidson & Weidley, 1976;Ponsluns, 1962). As the drug wears off, the avoidance response is restored (Wadenberg et al, 2001;Smith, Li, Becker, & Kapur, 2004).…”

Section: Introductionmentioning

confidence: 99%

A Computational Model of the Functional Role of the Ventral-Striatal D2 Receptor in the Expression of Previously Acquired Behaviors

2005

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The functional role of dopamine has attracted a great deal of interest ever since it was empirically discovered that dopamine-blocking drugs could be used to treat psychosis. Specifically, the D2 receptor and its expression in the ventral striatum have emerged as pivotal in our understanding of the complex role of the neuromodulator in schizophrenia, reward, and motivation. Our departure from the ubiquitous temporal difference (TD) model of dopamine neuron firing allows us to account for a range of experimental evidence suggesting that ventral striatal dopamine D2 receptor manipulation selectively modulates motivated behavior for distal versus proximal outcomes. Whether an internal model or the TD approach (or a mixture) is better suited to a comprehensive exposition of tonic and phasic dopamine will have important implications for our understanding of reward, motivation, schizophrenia, and impulsivity. We also use the model to help unite some of the leading cognitive hypotheses of dopamine function under a computational umbrella. We have used the model ourselves to stimulate and focus new rounds of experimental research.

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“…However, after several presentations of the CS-US pair, the animal typically runs during the CS and before the onset of the US, thereby avoiding the US altogether. Animals treated with low (noncataleptic) doses of APDs fail to perform avoidance responses to the CS, even though their escape response to the shock itself is relatively unaffected (Ader and Clink, 1957;Arnt, 1982;Cook and Catania, 1964;Cook and Weidley, 1957;Courvoisier, 1956;Davidson and Weidley, 1976;Ponsluns, 1962). This selective disruption of avoidance is characteristic of all APDs, but neither anxiolytics nor antidepressants show this effect (Courvoisier, 1956;Morpurgo, 1965;Reynolds and Czudek, 1995).…”

Section: Introductionmentioning

confidence: 99%

A Model of Antipsychotic Action in Conditioned Avoidance: A Computational Approach

Smith

Becker

et al. 2004

Neuropsychopharmacol

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The selective ability of antipsychotic drugs (APDs) to attenuate conditioned avoidance responding (CAR) has been recognized for over 50 years. However, most efforts to account for this finding have been either neurochemically oriented (focusing on the neuromodulator dopamine) or behavioral, with little effort invested in uniting the two within a computational model. In this paper we propose a computational model, based on concepts from formal reinforcement learning theory, which accounts for the basic finding that noncataleptic doses of APDs disrupt avoidance without disrupting escape. The model formally separates out sensory, motor, and reward processes, and makes novel predictions pertaining to the dose-and time-dependent effects of APDs on response latenciesFpredictions which we verified in experimental studies using four different APDs (haloperidol, chlorpromazine, risperidone, and clozapine). The APD action in this model is most consistent with an effect on 'expected future reward'Fan idea closely linked to motivational drives and consistent with several leading theories of dopamine action.

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Differential effects of neuroleptic and other psychotropic agents on acquisition of avoidance in rats

Cited by 83 publications

References 7 publications

YKP1447, A Novel Potential Atypical Antipsychotic Agent

YKP1447, A Novel Potential Atypical Antipsychotic Agent

A Computational Model of the Functional Role of the Ventral-Striatal D2 Receptor in the Expression of Previously Acquired Behaviors

A Model of Antipsychotic Action in Conditioned Avoidance: A Computational Approach

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