Blockade of intracranial self-stimulation by antipsychotic drugs: Failure to correlate with central alpha-noradrenergic blockade

Zarevics, Peter; Weidley, E. F.; Setler, Paulette E.

doi:10.1007/bf00492365

Cited by 44 publications

(6 citation statements)

References 33 publications

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“…There was a time when it seemed likely that activation of noradrenergic systems in the brain caused reward, but neither the anatomical nor the pharmacological evidence on which this view was based has held up in recent years. Drugs that selectively block noradrenergic receptors do not cause reward deficits in either the brain stimulation or the psychomotor stimulant reward paradigms of our group or those of others (deWit & Wise 1977;Fouriezos et al 1978;Risner & Jones 1976Yokel & Wise 1975, 1976Zarevics et al 1977). Close anatomical mapping of noradrenergic pathways does not link them to the anatomy of brain stimulation reward (Amaral & Routtenberg 1975;Clavier & Routtenberg 1974;Corbett & Wise 1979;Simon, Le Moal & Cardo 1975), and lesions of the noradrenergic pathways, once suspected of playing a role in brain stimulation reward phenomena, have failed to disrupt these phenomena (Clavier, Fibiger & Phillips 1976;Corbett, Skelton & Wise 1977;Koob, Balcom & Meyerhoff 1976).…”

Section: Hypotheses Of Neuroleptic Action: Levels Of Progressmentioning

confidence: 74%

Neuroleptics and operant behavior: The anhedonia hypothesis

1982

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Neuroleptic drugs disrupt the learning and performance of operant habits motivated by a variety of positive reinforcers, including food, water, brain stimulation, intravenous opiates, stimulants, and barbiturates. This disruption has been demonstrated in several kinds of experiments with doses that do not significantly limit normal response capacity. With continuous reinforcement neuroleptics gradually cause responding to cease, as in extinction or satiation. This pattern is not due to satiation, however, because it also occurs with nonsatiating reinforcement (such as saccharin or brain stimulation). Repeated tests with neuroleptics result in earlier and earlier response cessation reminiscent of the kind of decreased resistance to extinction caused by repeated tests without the expected reward. Indeed, withholding reward can have the same effect on responding under later neuroleptic treatment as prior experience with neuroleptics themselves; this suggests that there is a transfer of learning (really unlearning) from nonreward to neuroleptic conditions. These tests under continuous reinforcement schedules suggest that neuroleptics blunt the ability of reinforcers to sustain responding at doses which largely spare the ability of the animal to initiate responding. Animals trained under partial reinforcement, however, do not respond as well during neuroleptic testing as animals trained under continuous reinforcement. Thus, neuroleptics can also impair responding (though not response capacity) that is normally sustained by environmental stimuli (and associated expectancies) in the absence of the primary reinforcer. Neuroleptics also blunt the euphoric impact of amphetamine in humans. These data suggest that the most subtle and interesting effect of neuroleptics is a selective attenuation of motivational arousal which is (a) critical for goal-directed behavior, (b) normally induced by reinforcers and associated environmental stimuli, and (c) normally accompanied by the subjective experience of pleasure. Because these drugs are used to treat schizophrenia and because they cause parkinsonian-like side effects, this action has implications for a better understanding of human pathology as well as normal motivational processes.

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Section: Hypotheses Of Neuroleptic Action: Levels Of Progressmentioning

confidence: 74%

Neuroleptics and operant behavior: The anhedonia hypothesis

1982

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“…(±)7-OH-DPAT is selective for dopamine receptors but has activity at a 1 -and a 2 -adrenoceptors ( Timmermans et al 1984), although a-adrenoceptors do not play a critical role in self-stimulation behaviours (Zarevics et al 1977). The behavioural e¤ects of these compounds are therefore unlikely to be mediated through receptors other than dopaminergic receptors.…”

Section: Discussionmentioning

confidence: 98%

The effects of dopamine D 3 /D 2 receptor agonists on intracranial self stimulation in the rat

Hatcher

Hagan

1998

Psychopharmacology

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The effects of the dopamine D3/D2 receptor agonists quinpirole, quinelorane and (+/-)7-OH-DPAT [(+/-) 7-hydroxy-2(N,N-di-n-propylamino) tetralin] on intracranial self-stimulation (ICSS) were investigated. Rats implanted with bipolar electrodes into the lateral hypothalamus were trained to lever press on a continuous reinforcement schedule for positively reinforcing trains of electrical stimulation. Three measures of responding were calculated; the frequency at which responding was 50% of the maximum (M50), the asymptotic response rate and the total area under the curve (AUC) for each frequency sweep. Quinpirole (2.2-66.0 microg/kg SC) significantly increased M50 and reduced both asymptote and AUC. Quinelorane (0.25-79.0 microg/kg SC) had no significant effect on M50 values but significantly reduced both asymptote and AUC. (+/-)7-OH-DPAT (2.5-74.0 microg/kg) did not significantly affect any of the measures. The data show that low doses of quinpirole and quinelorane, but not (+/-)7-OH-DPAT, inhibit ICSS maintained by electrodes in the lateral hypothalamus. Either dopamine D2 or dopamine D3 receptor stimulation may play a role in mediating ICSS inhibition, but studies with more selective receptor agonists and antagonists are required to define the role of each receptor.

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“…If this were the case, then phenoxybenzamine should have produced extinction-like patterns of responding in this study. The dose range used was more than adequate; a 2 mg/kg injection is sufficient to block a central a-noradrenergically mediated flexor reflex, yet this and higher doses spare selfstimulation responding (Zarevics, Weidley, & Setler, 1977). It seems likely that the reward-attenuating property of neuroleptics is correctly attributed to the dopamineblocking action of these drugs.…”

Section: Discussionmentioning

confidence: 99%

Neuroleptic-induced attenuation of brain stimulation reward in rats.

Fouriezos¹,

Hansson²,

Wise³

1978

Journal of Comparative and Physiological Psychology

203

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In 30-min free-operant tests, the dopamine receptor blockers pimozide (.125, .25, and .50 mg/kg) and (-f-)-butaclamol (.1, .2, and .4 mg/kg) attenuated lever pressing for lateral hypothalamic brain stimulation. When discrete self-stimulation trials were offered in a straight alleyway, pimozide increased start box latencies, slowed running speeds, and reduced lever-pressing rates. However, performance early in both lever-pressing and runway sessions was normal; performance deteriorated as testing progressed, following patterns that paralleled those seen when animals were tested with reductions in the amplitude of stimulating current. Spontaneous recovery was obtained in both situations; experimenter-imposed 10-min time-outs caused renewed lever pressing and running. In contrast, a-noradrenergic receptor blockade by phenoxybenzamine (5,10, and 20 mg/kg) failed to produce extinction-like response patterns. These data support the view that central dopaminergic systems are important components of the neural mechanisms mediating reward.

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Blockade of intracranial self-stimulation by antipsychotic drugs: Failure to correlate with central alpha-noradrenergic blockade

Cited by 44 publications

References 33 publications

Neuroleptics and operant behavior: The anhedonia hypothesis

Neuroleptics and operant behavior: The anhedonia hypothesis

The effects of dopamine D 3 /D 2 receptor agonists on intracranial self stimulation in the rat

Neuroleptic-induced attenuation of brain stimulation reward in rats.

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