Mediated acquisition of a fear-motivated response and inhibitory effects of chlorpromazine

Davis, William S.; Capehart, Jack; Llewellin, W. L.

doi:10.1007/bf00411195

Cited by 15 publications

(6 citation statements)

References 10 publications

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“…The overall finding from the present study is consistent with our previous work on the motivational salience attenuation action of APDs (Li, Fletcher, 2007, Li, He, 2009, Zhang, Fang, 2011) as well as others (Beninger et al, 1980a, 1980b, Davis et al, 1961). Davis et al (1961) first trained rats to escape footshock in the shuttle box, then confined them in one side of the box and exposed them to 15 trials of the buzzer-footshock pairing under either chlorpromazine or saline.…”

Section: Discussionsupporting

confidence: 93%

“…Davis et al (1961) first trained rats to escape footshock in the shuttle box, then confined them in one side of the box and exposed them to 15 trials of the buzzer-footshock pairing under either chlorpromazine or saline. When tested without drug, the previously chlorpromazine-treated rats made significantly fewer avoidance responses than the saline rats, demonstrating that it was the action of chlorpromazine on the motivational salience of the buzzer that contributed to the lower avoidance in the chlorpromazine-treated rats.…”

Section: Discussionmentioning

confidence: 99%

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Avoidance disruptive effect of clozapine and olanzapine is potentiated by increasing the test trials: Further test of the motivational salience hypothesis

Feng

Song

2013

Pharmacology Biochemistry and Behavior

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Antipsychotic drugs suppress animals’ ability to avoid an aversive stimulus in the conditioned avoidance response model (CAR). This behavioral effect is thought to reflect antipsychotic activity and is suggested to be mediated by a drug’s action in attenuating the motivational salience of a conditioned stimulus (CS). In the present study, we tested whether atypical antipsychotic drugs clozapine and olanzapine act through this behavioral mechanism by manipulating the number of avoidance test trials. We reasoned that more CS trials in the present of clozapine or olanzapine would afford the drug more opportunities to decrease the motivational salience of the CS, thus avoidance decline would be greater with the increase of CS trials in each test session. In two separate experiments, adult male Sprague-Dawley rats were tested under clozapine (5.0 mg/kg, sc), olanzapine (0.5 mg/kg, sc) or vehicle (sterile water) for 6 consecutive days in three CS trial conditions (i.e. 3, 10, and 40 CS trials per session). Two days later, all rats were tested under the same 40-trial session after receiving clozapine (5.0 mg/kg, sc) or olanzapine (0.5 mg/kg, sc). Results show that repeated clozapine and olanzapine treatment persistently decreased avoidance response, and this effect was potentiated by the increase of number of CS trials in the test sessions, as the clozapine-treated or olanzapine-treated rats tested under the 40-trial or 10-trial condition had significantly lower avoidance and faster decline across-sessions than those tested under the 3-trial condition. This potentiated effect was not only seen in the total avoidance percentage, but also observed in the within-session decline pattern in the last three drug test sessions and in the final 40-trial test session. These findings suggest that the clinical efficacy of a drug can be enhanced by increasing the exposure of symptoms in the presence of the drug.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Avoidance disruptive effect of clozapine and olanzapine is potentiated by increasing the test trials: Further test of the motivational salience hypothesis

Feng

Song

2013

Pharmacology Biochemistry and Behavior

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“…These findings support the interpretation that the effect of the drug on exposure is critical to its effect in hastening fear extinction. This interpretation is consistent with other research (Davis et al, 1961;Hunt, 1956;Miller, 1961;Miller et al, 1957), since only those studies in which the drug increased exposure obtained an effect of more rapid fear extinction.…”

Section: Discussionsupporting

confidence: 93%

Effects of chlorpromazine on fear extinction.

Nelson¹

1967

Journal of Comparative and Physiological Psychology

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“…However, the common behavioral or psychological processes are currently unknown. For example, existing hypotheses of why APDs disrupt avoidance include the inhibition of an internal "fear" or "anxiety" (Cook & Weidley, 1957;Miller, Murphy, & Mirsky, 1957;Davis, Capehart, & Llewellin, 1961;Hunt, 1956), motor impairment (Ponsluns, 1962;Cook & Catania, 1964;Morpurgo, 1965;Beninger, Mason, Phillips, & Fibiger, 1980a, 1980bGrilly et al, 1984;Aguilar, Mari-Sanmillan, Mortant-Deusa, & Minarro, 2000;Ogren & Archer, 1994), reduced responsiveness to external stimuli (Dews & Morse, 1961), decrease in sensory stimulation (Irwin, 1958;Key, 1961), and loss of attention or arousal (Low, Eliasson, & Kornetsky, 1966). However, following the incentive salience hypothesis of dopamine function, we will propose a motivational explanation that can subsequently be used to account for additional data from other experimental paradigms.…”

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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Mediated acquisition of a fear-motivated response and inhibitory effects of chlorpromazine

Cited by 15 publications

References 10 publications

Avoidance disruptive effect of clozapine and olanzapine is potentiated by increasing the test trials: Further test of the motivational salience hypothesis

Avoidance disruptive effect of clozapine and olanzapine is potentiated by increasing the test trials: Further test of the motivational salience hypothesis

Effects of chlorpromazine on fear extinction.

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

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