Effects of intermittent and continuous cocaine administration on dopamine release and uptake regulation in the striatum: in vitro voltammetric assessment.

Published

Journal Article

Chronic daily injections of cocaine induce behavioral sensitization to subsequent cocaine challenge, while continuous infusion induces tolerance. Following a 7-day withdrawal period, we examined the effects of these two dosing regimens on: (1) baseline dopamine efflux and uptake following single-pulse electrical stimulation, (2) inhibition of uptake by cocaine; and (3) inhibition of efflux by autoreceptor activation. Cocaine (40 mg/kg per day) was administered to rats for 14 days either continuously by osmotic minipumps or intermittently by once-a-day injections. Minipumps containing saline were implanted in the control group. After 7 days of withdrawal, dopamine kinetics in the caudate was examined using in vitro fast-scan cyclic voltammetry. This technique provides very rapid measurements of dopamine in the extracellular space. Thus, when combined with endogenous dopamine efflux evoked by single-pulse, electrical stimulations, it was possible directly to measure the release and uptake components of the efflux. In the absence of pharmacological agents, no group differences were found in the amount of baseline dopamine released or in the uptake kinetics; the potency of bath-applied cocaine (0.03-60 microM) in inhibiting the uptake was also unaltered in either group. In contrast, the potency of quinpirole (an autoreceptor agonist, 5-250 nM) was significantly decreased and increased in the cocaine injection and pump groups, respectively. Thus, the cocaine administration regimen which produces sensitization results in a functional subsensitivity of release-modulating autoreceptors, while the tolerance-producing regimen results in autoreceptor supersensitivity.

Full Text

Cited Authors

  • Jones, SR; Lee, TH; Wightman, RM; Ellinwood, EH

Published Date

  • August 1996

Published In

Volume / Issue

  • 126 / 4

Start / End Page

  • 331 - 338

PubMed ID

  • 8878349

Pubmed Central ID

  • 8878349

Electronic International Standard Serial Number (EISSN)

  • 1432-2072

International Standard Serial Number (ISSN)

  • 0033-3158

Digital Object Identifier (DOI)

  • 10.1007/bf02247384

Language

  • eng