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Effects of catecholamine-depleting drugs and amphetamine on self-stimulation of brain following various 6-hydroxydopamine treatments

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Abstract

Changes in electrical self-stimulation responding were examined in rats with electrodes implanted in the lateral hypothalamus following 6-hydroxydopamine treatments which depleted brain dopamine, norepinephrine or both of these catecholamines. Acute depression of self-stimulation occurred after treatments which reduced brain dopamine, but did not occur in rats treated to deplete just brain norepinephrine. A chronic deficit in self-stimulation responding occurred in rats treated with 6-hydroxydopamine in combination with pargyline to reduce both brain amines, while responding of animals in which brain dopamine was reduced returned to levels observed prior to 6-hydroxydopamine treatment. A dose of α-methyl-tyrosine (25 mg/kg), which did not affect responding of control rats, caused a significant reduction in responding of rats depleted of brain dopamine. This treatment did not affect responding of rats depleted of brain norepinephrine. Administration of the dopamine-Β-hydroxylase inhibitor, U-14624, failed to affect self-stimulation in spite of an additional 70% reduction of brain norepinephrine content. The response to a dose of d-amphetamine (0.25 mg/kg), that increased self-stimulation of control rats, was significantly reduced in rats with brain dopamine selectively depleted. Rats in which norepinephrine was depleted responded to d-amphetamine like the control group. α-Methyltyrosine antagonized the increased self-stimulation responding following administration of d-amphetamine (1 mg/kg) to reserpinized rats, while U-14624 did not. Results support the hypothesis that central dopaminergic fibers have an important involvement in the maintenance of self-stimulation of brain.

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Authors and Affiliations

  1. Departments of Pharmacology and Psychiatry, Biological Sciences Research Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina

    Barrett R. Cooper, Jerry M. Cott & George R. Breese

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  1. Barrett R. Cooper
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  2. Jerry M. Cott
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  3. George R. Breese
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Cooper, B.R., Cott, J.M. & Breese, G.R. Effects of catecholamine-depleting drugs and amphetamine on self-stimulation of brain following various 6-hydroxydopamine treatments. Psychopharmacologia 37, 235–248 (1974). https://doi.org/10.1007/BF00421537

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  • DOI: https://doi.org/10.1007/BF00421537

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