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Amphetamine elicits opposing actions on readily releasable and reserve pools for dopamine.

Covey DP, Juliano SA, Garris PA - PLoS ONE (2013)

Bottom Line: These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses.A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only.Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, Illinois State University, Normal, Illinois, USA.

ABSTRACT
Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent in the dorsal striatum. Specifically, amphetamine up-regulated vesicular dopamine release elicited by a short-duration train, which interrogates the readily releasable pool, but depleted release elicited by a long-duration train, which interrogates the reserve pool. These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses. A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only. We submit that amphetamine differentially targeting dopamine stores reconciles the paradoxical activation of tonic and phasic dopamine signaling. Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties.

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Related in: MedlinePlus

Representative effects of AMPH on tonic dopamine levels in the dorsal striatum.The black line (left y axis) in the top panel shows background-subtracted current, and pseudocolor plot underneath displays all background-subtracted cyclic voltammograms immediately following administration of the high dose (10 mg/kg) of AMPH. Current, which was measured at the peak oxidative potential for dopamine (horizontal white line on the pseudocolor plot), was converted to dopamine concentration (red line, right y axis) using PCR. INSET. Background-subtracted cyclic voltammograms taken at 150 s and 250 s (blue arrows, blue line) and from the post-drug electrically evoked (60 Hz, 0.4 s) dopamine signal (black line).
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pone-0060763-g005: Representative effects of AMPH on tonic dopamine levels in the dorsal striatum.The black line (left y axis) in the top panel shows background-subtracted current, and pseudocolor plot underneath displays all background-subtracted cyclic voltammograms immediately following administration of the high dose (10 mg/kg) of AMPH. Current, which was measured at the peak oxidative potential for dopamine (horizontal white line on the pseudocolor plot), was converted to dopamine concentration (red line, right y axis) using PCR. INSET. Background-subtracted cyclic voltammograms taken at 150 s and 250 s (blue arrows, blue line) and from the post-drug electrically evoked (60 Hz, 0.4 s) dopamine signal (black line).

Mentions: Figure 5 shows a representative background-subtracted FSCV recording (black) collected immediately surrounding the time of injecting high-dose AMPH. This non-electrically evoked trace, representing current measured at the peak oxidative potential for dopamine (i.e., along the horizontal white line of the pseudocolor plot below), gradually increases across the 5-min epoch. Individual voltammograms collected along the two vertical white lines of the pseudocolor plot (blue) are overlaid with a dopamine voltammogram collected during electrical stimulation (black) earlier in this recording (data not shown). While there is evidence for dopamine in the individual voltammograms and in the sequential voltammograms displayed in the pseudocolor plot for this non-electrically evoked trace, other analytes obscure its selective measurement with FSCV alone. However, PCR (red) resolves the dopamine component of this FSCV recording, demonstrating an activation of tonic dopamine signaling by AMPH.


Amphetamine elicits opposing actions on readily releasable and reserve pools for dopamine.

Covey DP, Juliano SA, Garris PA - PLoS ONE (2013)

Representative effects of AMPH on tonic dopamine levels in the dorsal striatum.The black line (left y axis) in the top panel shows background-subtracted current, and pseudocolor plot underneath displays all background-subtracted cyclic voltammograms immediately following administration of the high dose (10 mg/kg) of AMPH. Current, which was measured at the peak oxidative potential for dopamine (horizontal white line on the pseudocolor plot), was converted to dopamine concentration (red line, right y axis) using PCR. INSET. Background-subtracted cyclic voltammograms taken at 150 s and 250 s (blue arrows, blue line) and from the post-drug electrically evoked (60 Hz, 0.4 s) dopamine signal (black line).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643976&req=5

pone-0060763-g005: Representative effects of AMPH on tonic dopamine levels in the dorsal striatum.The black line (left y axis) in the top panel shows background-subtracted current, and pseudocolor plot underneath displays all background-subtracted cyclic voltammograms immediately following administration of the high dose (10 mg/kg) of AMPH. Current, which was measured at the peak oxidative potential for dopamine (horizontal white line on the pseudocolor plot), was converted to dopamine concentration (red line, right y axis) using PCR. INSET. Background-subtracted cyclic voltammograms taken at 150 s and 250 s (blue arrows, blue line) and from the post-drug electrically evoked (60 Hz, 0.4 s) dopamine signal (black line).
Mentions: Figure 5 shows a representative background-subtracted FSCV recording (black) collected immediately surrounding the time of injecting high-dose AMPH. This non-electrically evoked trace, representing current measured at the peak oxidative potential for dopamine (i.e., along the horizontal white line of the pseudocolor plot below), gradually increases across the 5-min epoch. Individual voltammograms collected along the two vertical white lines of the pseudocolor plot (blue) are overlaid with a dopamine voltammogram collected during electrical stimulation (black) earlier in this recording (data not shown). While there is evidence for dopamine in the individual voltammograms and in the sequential voltammograms displayed in the pseudocolor plot for this non-electrically evoked trace, other analytes obscure its selective measurement with FSCV alone. However, PCR (red) resolves the dopamine component of this FSCV recording, demonstrating an activation of tonic dopamine signaling by AMPH.

Bottom Line: These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses.A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only.Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, Illinois State University, Normal, Illinois, USA.

ABSTRACT
Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent in the dorsal striatum. Specifically, amphetamine up-regulated vesicular dopamine release elicited by a short-duration train, which interrogates the readily releasable pool, but depleted release elicited by a long-duration train, which interrogates the reserve pool. These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses. A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only. We submit that amphetamine differentially targeting dopamine stores reconciles the paradoxical activation of tonic and phasic dopamine signaling. Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties.

Show MeSH
Related in: MedlinePlus