Behavioral and neurochemical effects of amphetamine analogs that release monoamines in the squirrel monkey

Heather L. Kimmel, Daniel F. Manvich, Bruce E. Blough, S. Stevens Negus, Leonard L. Howell

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

To date, there are no effective pharmacotherapies for treating psychostimulant abuse. Previous preclinical and clinical studies have shown that continuous treatment with the monoamine releaser amphetamine reduces cocaine self-administration, but amphetamine selectively targets the dopamine system and is reinforcing. In the present study, we examined the consequences of administration of amphetamine and three structurally related analogs that vary in their potencies for releasing dopamine and serotonin on behavioral-stimulant effects and nucleus accumbens dopamine levels in squirrel monkeys. Amphetamine and PAL-353, which have relatively high selectivity for releasing dopamine vs. serotonin, increased accumbens dopamine levels and induced stimulant effects on behavior maintained by a fixed-interval schedule of reinforcement. PAL-313, which has a relatively low selectivity for releasing dopamine vs. serotonin, increased dopamine levels, but did not induce behavioral-stimulant effects. PAL-287, which is relatively nonselective in releasing dopamine and serotonin, did not increase dopamine levels or induce behavioral-stimulant effects. These results demonstrate that increasing serotonergic activity attenuates dopamine release and dopamine-mediated behavioral effects of monoamine releasers. In addition, these results support further investigation of PAL-313 and similar compounds as a potential medication for treating psychostimulant abuse.

Original languageEnglish (US)
Pages (from-to)278-284
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume94
Issue number2
DOIs
StatePublished - Dec 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry
  • Biochemistry
  • Behavioral Neuroscience
  • Clinical Biochemistry
  • Toxicology
  • Pharmacology

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