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Central and peripheral contributions to dynamic changes in nucleus accumbens glucose induced by intravenous cocaine.

Wakabayashi KT, Kiyatkin EA - Front Neurosci (2015)

Bottom Line: The pattern of neural, physiological and behavioral effects induced by cocaine is consistent with metabolic neural activation, yet direct attempts to evaluate central metabolic effects of this drug have produced controversial results.While the rapid, phasic component of the glucose response remained stable following subsequent cocaine injections, the tonic component progressively decreased.However, this analog did not induce increases in either locomotion or tonic glucose, suggesting direct central mediation of these cocaine effects.

View Article: PubMed Central - PubMed

Affiliation: Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, DHHS Baltimore, MD, USA.

ABSTRACT
The pattern of neural, physiological and behavioral effects induced by cocaine is consistent with metabolic neural activation, yet direct attempts to evaluate central metabolic effects of this drug have produced controversial results. Here, we used enzyme-based glucose sensors coupled with high-speed amperometry in freely moving rats to examine how intravenous cocaine at a behaviorally active dose affects extracellular glucose levels in the nucleus accumbens (NAc), a critical structure within the motivation-reinforcement circuit. In drug-naive rats, cocaine induced a bimodal increase in glucose, with the first, ultra-fast phasic rise appearing during the injection (latency 6-8 s; ~50 μM or ~5% of baseline) followed by a larger, more prolonged tonic elevation (~100 μM or 10% of baseline, peak ~15 min). While the rapid, phasic component of the glucose response remained stable following subsequent cocaine injections, the tonic component progressively decreased. Cocaine-methiodide, cocaine's peripherally acting analog, induced an equally rapid and strong initial glucose rise, indicating cocaine's action on peripheral neural substrates as its cause. However, this analog did not induce increases in either locomotion or tonic glucose, suggesting direct central mediation of these cocaine effects. Under systemic pharmacological blockade of dopamine transmission, both phasic and tonic components of the cocaine-induced glucose response were only slightly reduced, suggesting a significant role of non-dopamine mechanisms in cocaine-induced accumbal glucose influx. Hence, intravenous cocaine induces rapid, strong inflow of glucose into NAc extracellular space by involving both peripheral and central, non-dopamine drug actions, thus preventing a possible deficit resulting from enhanced glucose use by brain cells.

No MeSH data available.


Related in: MedlinePlus

Histological locations of electrochemical sensors. Locations of the active area of Glucose (red) and Null (blue) sensors used in this study shown with the stereotaxic coordinates of Paxinos and Watson (1998). While the sensors were equally implanted in both sides of the brain, for clarity, glucose sensors are shown on the right and  sensors are shown on the left hemispheres.
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Figure 8: Histological locations of electrochemical sensors. Locations of the active area of Glucose (red) and Null (blue) sensors used in this study shown with the stereotaxic coordinates of Paxinos and Watson (1998). While the sensors were equally implanted in both sides of the brain, for clarity, glucose sensors are shown on the right and sensors are shown on the left hemispheres.

Mentions: Our previous studies suggest significant between-structure differences in glucose responses (Kiyatkin and Lenoir, 2012). Therefore, in this study it was critical to carefully examine the location of the recording sensors and exclude all cases where sensor tips were localized out of the target area. As can be seen in Figure 8, all sensors in rats included in our data set were closely localized within the NAc shell with relatively small dorso-ventral and anterior-posterior variability. Rats (n = 5), where the sensors were localized out of the target area were excluded from data analyses. While the number of rats in each group did not allow for a rigorous statistical evaluation of anterior-posterior differences in glucose responses, there were no evident differences along this axis of the NAc shell.


Central and peripheral contributions to dynamic changes in nucleus accumbens glucose induced by intravenous cocaine.

Wakabayashi KT, Kiyatkin EA - Front Neurosci (2015)

Histological locations of electrochemical sensors. Locations of the active area of Glucose (red) and Null (blue) sensors used in this study shown with the stereotaxic coordinates of Paxinos and Watson (1998). While the sensors were equally implanted in both sides of the brain, for clarity, glucose sensors are shown on the right and  sensors are shown on the left hemispheres.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325903&req=5

Figure 8: Histological locations of electrochemical sensors. Locations of the active area of Glucose (red) and Null (blue) sensors used in this study shown with the stereotaxic coordinates of Paxinos and Watson (1998). While the sensors were equally implanted in both sides of the brain, for clarity, glucose sensors are shown on the right and sensors are shown on the left hemispheres.
Mentions: Our previous studies suggest significant between-structure differences in glucose responses (Kiyatkin and Lenoir, 2012). Therefore, in this study it was critical to carefully examine the location of the recording sensors and exclude all cases where sensor tips were localized out of the target area. As can be seen in Figure 8, all sensors in rats included in our data set were closely localized within the NAc shell with relatively small dorso-ventral and anterior-posterior variability. Rats (n = 5), where the sensors were localized out of the target area were excluded from data analyses. While the number of rats in each group did not allow for a rigorous statistical evaluation of anterior-posterior differences in glucose responses, there were no evident differences along this axis of the NAc shell.

Bottom Line: The pattern of neural, physiological and behavioral effects induced by cocaine is consistent with metabolic neural activation, yet direct attempts to evaluate central metabolic effects of this drug have produced controversial results.While the rapid, phasic component of the glucose response remained stable following subsequent cocaine injections, the tonic component progressively decreased.However, this analog did not induce increases in either locomotion or tonic glucose, suggesting direct central mediation of these cocaine effects.

View Article: PubMed Central - PubMed

Affiliation: Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, DHHS Baltimore, MD, USA.

ABSTRACT
The pattern of neural, physiological and behavioral effects induced by cocaine is consistent with metabolic neural activation, yet direct attempts to evaluate central metabolic effects of this drug have produced controversial results. Here, we used enzyme-based glucose sensors coupled with high-speed amperometry in freely moving rats to examine how intravenous cocaine at a behaviorally active dose affects extracellular glucose levels in the nucleus accumbens (NAc), a critical structure within the motivation-reinforcement circuit. In drug-naive rats, cocaine induced a bimodal increase in glucose, with the first, ultra-fast phasic rise appearing during the injection (latency 6-8 s; ~50 μM or ~5% of baseline) followed by a larger, more prolonged tonic elevation (~100 μM or 10% of baseline, peak ~15 min). While the rapid, phasic component of the glucose response remained stable following subsequent cocaine injections, the tonic component progressively decreased. Cocaine-methiodide, cocaine's peripherally acting analog, induced an equally rapid and strong initial glucose rise, indicating cocaine's action on peripheral neural substrates as its cause. However, this analog did not induce increases in either locomotion or tonic glucose, suggesting direct central mediation of these cocaine effects. Under systemic pharmacological blockade of dopamine transmission, both phasic and tonic components of the cocaine-induced glucose response were only slightly reduced, suggesting a significant role of non-dopamine mechanisms in cocaine-induced accumbal glucose influx. Hence, intravenous cocaine induces rapid, strong inflow of glucose into NAc extracellular space by involving both peripheral and central, non-dopamine drug actions, thus preventing a possible deficit resulting from enhanced glucose use by brain cells.

No MeSH data available.


Related in: MedlinePlus