Microinjection of the D2 agonist quinpirole into the A10 dopamine region blocks amphetamine-, but not cocaine-stimulated motor activity

Jeffery Steketee, P. W. Kalivas

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Abstract

Dopamine neurons in the ventral mesencephalon are under the inhibitory influence of dopamine D2 and γ-aminobutyric acid(B) receptors. In a previous report, we demonstrated that intra-A10 injections of baclofen, a γ- aminobutyric acid(B) agonist, could inhibit the motor-stimulant response to cocaine and amphetamine. In order to further extend these results, we examined the effects of injection of the D2 agonist quinpirole into the A10 region on cocaine- and amphetamine-stimulated motor activity. The results of this study showed that intra-A10 quinpirole dose-dependently decreased locomotor activity. In addition, an intra-A10 injection of 0.3 nmol/μl quinpirole, a dose chosen for its near threshold effect, could block the motor-stimulant response to a low dose of amphetamine (0.5 mg/kg) and attenuate the response to moderate doses (1.0 and 2.0 mg/kg). Cocaine- stimulated motor activity, at all doses tested (7.5, 15.0 and 30.0 mg/kg), was not altered by intra-A10 quinpirole pretreatment. In vivo microdialysis revealed that quinpirole was unable to block the amphetamine-induced increase in extracellular dopamine concentrations within the nucleus accumbens, despite blocking the motor-stimulant response. It is suggested that the different mechanisms of action of cocaine and amphetamine, uptake blocker vs. releaser or longloop vs. shortloop feedback inhibition of A10 dopamine neurons, respectively, may account for the differential effects that quinpirole had in blocking the motor-stimulant response to these psychostimulants.

Original languageEnglish (US)
Pages (from-to)811-818
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume261
Issue number2
StatePublished - Jan 1 1992

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Quinpirole
antineoplaston A10
Microinjections
Amphetamine
Cocaine
Dopamine
Motor Activity
Aminobutyrates
Dopaminergic Neurons
Injections
Baclofen
Microdialysis
Nucleus Accumbens
Locomotion
Mesencephalon

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

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abstract = "Dopamine neurons in the ventral mesencephalon are under the inhibitory influence of dopamine D2 and γ-aminobutyric acid(B) receptors. In a previous report, we demonstrated that intra-A10 injections of baclofen, a γ- aminobutyric acid(B) agonist, could inhibit the motor-stimulant response to cocaine and amphetamine. In order to further extend these results, we examined the effects of injection of the D2 agonist quinpirole into the A10 region on cocaine- and amphetamine-stimulated motor activity. The results of this study showed that intra-A10 quinpirole dose-dependently decreased locomotor activity. In addition, an intra-A10 injection of 0.3 nmol/μl quinpirole, a dose chosen for its near threshold effect, could block the motor-stimulant response to a low dose of amphetamine (0.5 mg/kg) and attenuate the response to moderate doses (1.0 and 2.0 mg/kg). Cocaine- stimulated motor activity, at all doses tested (7.5, 15.0 and 30.0 mg/kg), was not altered by intra-A10 quinpirole pretreatment. In vivo microdialysis revealed that quinpirole was unable to block the amphetamine-induced increase in extracellular dopamine concentrations within the nucleus accumbens, despite blocking the motor-stimulant response. It is suggested that the different mechanisms of action of cocaine and amphetamine, uptake blocker vs. releaser or longloop vs. shortloop feedback inhibition of A10 dopamine neurons, respectively, may account for the differential effects that quinpirole had in blocking the motor-stimulant response to these psychostimulants.",
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T1 - Microinjection of the D2 agonist quinpirole into the A10 dopamine region blocks amphetamine-, but not cocaine-stimulated motor activity

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AU - Kalivas, P. W.

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N2 - Dopamine neurons in the ventral mesencephalon are under the inhibitory influence of dopamine D2 and γ-aminobutyric acid(B) receptors. In a previous report, we demonstrated that intra-A10 injections of baclofen, a γ- aminobutyric acid(B) agonist, could inhibit the motor-stimulant response to cocaine and amphetamine. In order to further extend these results, we examined the effects of injection of the D2 agonist quinpirole into the A10 region on cocaine- and amphetamine-stimulated motor activity. The results of this study showed that intra-A10 quinpirole dose-dependently decreased locomotor activity. In addition, an intra-A10 injection of 0.3 nmol/μl quinpirole, a dose chosen for its near threshold effect, could block the motor-stimulant response to a low dose of amphetamine (0.5 mg/kg) and attenuate the response to moderate doses (1.0 and 2.0 mg/kg). Cocaine- stimulated motor activity, at all doses tested (7.5, 15.0 and 30.0 mg/kg), was not altered by intra-A10 quinpirole pretreatment. In vivo microdialysis revealed that quinpirole was unable to block the amphetamine-induced increase in extracellular dopamine concentrations within the nucleus accumbens, despite blocking the motor-stimulant response. It is suggested that the different mechanisms of action of cocaine and amphetamine, uptake blocker vs. releaser or longloop vs. shortloop feedback inhibition of A10 dopamine neurons, respectively, may account for the differential effects that quinpirole had in blocking the motor-stimulant response to these psychostimulants.

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