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J Prowse

Publications and source records attributed to J Prowse.

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Comparative effects of beta 2-adrenoceptor agonists on intracranial self-stimulation, Sidman avoidance, and motor activity in rats.

The effects of beta-adrenoceptor agonists were compared in various operant behavioral tasks, particularly intracranial self-stimulation (ICSS). Clenbuterol, salbutamol, and terbutaline all reduced responding by rats that lever-pressed for low stimulation intensities. The effects of clenbuterol in this test were completely reversed by propranolol, and those of salbutamol were partly reversed. Intermediate doses of clenbuterol and salbutamol slowed the initiation of rewarding brain stimulation in a shuttlebox but had little or no effect on the termination latencies. However, higher doses of both drugs lengthened the termination latencies. Motor activity was reduced at doses that attenuated ICSS responding. Complete tolerance occurred within 4 days to the effects of clenbuterol and salbutamol on lever-pressing ICSS and to the effects of clenbuterol on motor activity. The apparent performance deficits induced by these drugs were overcome by more intense motivation. For example, even at high doses, clenbuterol reduced ICSS lever-pressing only partially when animals bar-pressed for high rather than low stimulation intensities. Furthermore, all three drugs failed to alter Sidman avoidance responding at doses up to 100 times those that attenuated ICSS responding. It is concluded that although beta-adrenoceptor agonists cause apparent sedation in rats, this sedation is limited and shows rapid tolerance.

Adrenergic beta-Agonists↗

Effects of various catecholamine receptor antagonists, muscle relaxation and physical hindrance on shuttlebox self-stimulation.

Certain drugs, particularly clozapine and clonidine, have been reported to increase selectively the latency to initiate brain stimulation (the ON latency) in a shuttlebox test of self-stimulation, suggesting a preferential attenuation of the "reward" component. The pharmacological selectivity of this reported effect was systematically evaluated. At doses that blocked bar-pressing self-stimulation, metoclopramide (3 mg/kg), prazosin (3 mg/kg) clonidine (0.1mg/kg), clozapine (3 mg/kg)and haloperidol (0.3 mg/kg), all elevated the ON latency to a greater extent than the OFF latency. Methocarbamol (200 mg/kg), and a muscle relaxant, also elevated the ON latency preferentially but the magnitude of this preferential effect was smaller than that produced by the other drugs. A hurdle in the center of the shuttlebox increased the ON and OFF latencies nonselectively. The shuttlebox procedure does not clearly discriminate among various substances that interfere with noradrenergic or dopaminergic neurotransmission, but the common profile produced by the these substances is distinguishable to some degree from simple motor disruption.

Adrenergic alpha-Antagonists↗

Differential effects of d-amphetamine, pipradrol and bupropion on shuttlebox self-stimulation.

The shuttlebox self-stimulation test is claimed by Atrens to differentiate drug effects on brain stimulation reward from those on performance variables. Thus, for example, drug-induced enhancement of the reward value of stimulation should be reflected in a selective reduction of the latency to initiate stimulation (the ON latency), as compared with the latency to terminate stimulation (the OFF latency). The effects of the psychostimulant drugs, d-amphetamine and pipradrol, and the antidepressant, bupropion, were evaluated in this procedure as well as in a bar-pressing test of self-stimulation. Pipradrol (3 and 10 mg/kg) and bupropion (54 mg/kg) reduced ON latencies by 40% or more but failed to shorten OFF latencies, indicating that performance variables were not involved in the ON latency decrements. Although d-amphetamine (0.3 and 1.0 mg/kg) shortened ON latencies, the 1.0 mg/kg dose also reduced OFF latencies. Drug doses that reduced ON latencies also increased bar-pressing self-stimulation. The shuttlebox self-stimulation test appears to be capable of discriminating drug-induced enhancement in brain stimulation reward from performance variables.

Animals↗

Anxiolytic drugs selectively increase preferred duration of rewarding brain stimulation in a shuttlebox test.

In the shuttlebox self-stimulation test described by Atrens, rewarding brain stimulation is independently initiated and terminated by rats. I has been hypothesized that gradually accumulating aversiveness of stimulation motivates the rat to terminate the rewarding stimulation train. In agreement with this view, optimal doses of the known anxiolytics, pentobarbital (5 and 10 mg/kg) diazepam (1 and 2.5 mg/kg), chlordiazepoxide (3 and 5.4 mg/kg) and CL 218,872 (3, 10 and 30 mg/kg) preferentially increased the latency to terminate stimulation (the OFF latency), as compared with the latency to initiate stimulation (the ON latency). Higher doses increased both latencies in a nonselective fashion, suggesting nonselective performance impairment. The shuttlebox self-stimulation test constitutes a potentially useful measure of experimental approach-avoidance conflict, with the OFF latency indicating anticonflict activity and the ON latency providing a control for performance variables.

Animals↗

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Humans↗