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Methylenedioxypyrovalerone (MDPV) mimics cocaine in its physiological and behavioral effects but induces distinct changes in NAc glucose.

Wakabayashi KT, Ren SE, Kiyatkin EA - Front Neurosci (2015)

Bottom Line: Using enzyme-based glucose sensors coupled with amperometery in freely moving rats, we found that MDPV tonically decreases NAc glucose levels, a response that is opposite to what we previously observed with cocaine.By analyzing Skin-Muscle temperature differentials, a valid measure of skin vascular tone, we found that MDPV induces vasoconstriction; a similar effect at the level of cerebral vessels could be responsible for the MDPV-induced decrease in NAc glucose.While cocaine also induced comparable, if not slightly stronger peripheral vasoconstriction, this effect was overpowered by local neural activity-induced vasodilation, resulting in rapid surge in NAc glucose.

View Article: PubMed Central - PubMed

Affiliation: In-Vivo Electrophysiology Unit, Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, Department of Health and Human Services, National Institutes of Health Baltimore, MD, USA.

ABSTRACT
Methylenedioxypyrovalerone (MDPV) is generally considered to be a more potent cocaine-like psychostimulant, as it shares a similar pharmacological profile with cocaine and induces similar physiological and locomotor responses. Recently, we showed that intravenous cocaine induces rapid rise in nucleus accumbens (NAc) glucose and established its relation to neural activation triggered by the peripheral drug actions. This study was conducted to find out whether MDPV, at a behaviorally equivalent dose, shares a similar pattern of NAc glucose dynamics. Using enzyme-based glucose sensors coupled with amperometery in freely moving rats, we found that MDPV tonically decreases NAc glucose levels, a response that is opposite to what we previously observed with cocaine. By analyzing Skin-Muscle temperature differentials, a valid measure of skin vascular tone, we found that MDPV induces vasoconstriction; a similar effect at the level of cerebral vessels could be responsible for the MDPV-induced decrease in NAc glucose. While cocaine also induced comparable, if not slightly stronger peripheral vasoconstriction, this effect was overpowered by local neural activity-induced vasodilation, resulting in rapid surge in NAc glucose. These results imply that cocaine-users may be more susceptible to addiction than MDPV-users due to the presence of an interoceptive signal (i.e., sensory cue), which may result in earlier and more direct reward detection. Additionally, while health complications arising from acute cocaine use are typically cardiovascular related, MDPV may be more dangerous to the brain due to uncompensated cerebral vasoconstriction.

No MeSH data available.


Related in: MedlinePlus

Correlative relationships between changes in NAc glucose, temperature parameters and locomotion. Pearson correlation coefficients and linear regression were calculated for all animals in all experimental sessions using mean, high-resolution (10-s bins) data and an analysis window of 360-s post-injection. Unfilled points labeled 1–5 represent the first five time points (-10 to 30 s) and correspond with effect latency. (A–C) show highly significant (p < 0.0001) and tight correlations between MDPV-induced changes in NAc [glucose] and (A) Skin-Muscle differential (r = 0.99, y = 0.028x - 0.104), (B) NAc-Muscle differential (r = −0.98, y = −0.007x + 0.025), and (C) locomotion (−0.84, y = −0.185x + 1.959). Data for cocaine is organized in parallel, with (D–F) displaying cocaine-induced NAc [glucose] changes vs. the same three parameters described above. R-values and linear regression are not shown for cocaine because of absence of correlation. Open circles with numbers are values for initial five time points (50 s) post-injection.
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Figure 7: Correlative relationships between changes in NAc glucose, temperature parameters and locomotion. Pearson correlation coefficients and linear regression were calculated for all animals in all experimental sessions using mean, high-resolution (10-s bins) data and an analysis window of 360-s post-injection. Unfilled points labeled 1–5 represent the first five time points (-10 to 30 s) and correspond with effect latency. (A–C) show highly significant (p < 0.0001) and tight correlations between MDPV-induced changes in NAc [glucose] and (A) Skin-Muscle differential (r = 0.99, y = 0.028x - 0.104), (B) NAc-Muscle differential (r = −0.98, y = −0.007x + 0.025), and (C) locomotion (−0.84, y = −0.185x + 1.959). Data for cocaine is organized in parallel, with (D–F) displaying cocaine-induced NAc [glucose] changes vs. the same three parameters described above. R-values and linear regression are not shown for cocaine because of absence of correlation. Open circles with numbers are values for initial five time points (50 s) post-injection.

Mentions: Since changes in [glucose] are determined by changes in metabolic activity and vessel tone, next we examined the relationships between drug-induced glucose responses, NAc-Muscle and Skin-Muscle differentials, two indices that reflect intra-brain heat accumulation due to metabolic activation and the state of skin vessels, respectively; the analysis window in this case was defined from the moment of drug injection (0 s) to the peak effect of MDPV on NAc glucose (360 s) (Figure 7).


Methylenedioxypyrovalerone (MDPV) mimics cocaine in its physiological and behavioral effects but induces distinct changes in NAc glucose.

Wakabayashi KT, Ren SE, Kiyatkin EA - Front Neurosci (2015)

Correlative relationships between changes in NAc glucose, temperature parameters and locomotion. Pearson correlation coefficients and linear regression were calculated for all animals in all experimental sessions using mean, high-resolution (10-s bins) data and an analysis window of 360-s post-injection. Unfilled points labeled 1–5 represent the first five time points (-10 to 30 s) and correspond with effect latency. (A–C) show highly significant (p < 0.0001) and tight correlations between MDPV-induced changes in NAc [glucose] and (A) Skin-Muscle differential (r = 0.99, y = 0.028x - 0.104), (B) NAc-Muscle differential (r = −0.98, y = −0.007x + 0.025), and (C) locomotion (−0.84, y = −0.185x + 1.959). Data for cocaine is organized in parallel, with (D–F) displaying cocaine-induced NAc [glucose] changes vs. the same three parameters described above. R-values and linear regression are not shown for cocaine because of absence of correlation. Open circles with numbers are values for initial five time points (50 s) post-injection.
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Figure 7: Correlative relationships between changes in NAc glucose, temperature parameters and locomotion. Pearson correlation coefficients and linear regression were calculated for all animals in all experimental sessions using mean, high-resolution (10-s bins) data and an analysis window of 360-s post-injection. Unfilled points labeled 1–5 represent the first five time points (-10 to 30 s) and correspond with effect latency. (A–C) show highly significant (p < 0.0001) and tight correlations between MDPV-induced changes in NAc [glucose] and (A) Skin-Muscle differential (r = 0.99, y = 0.028x - 0.104), (B) NAc-Muscle differential (r = −0.98, y = −0.007x + 0.025), and (C) locomotion (−0.84, y = −0.185x + 1.959). Data for cocaine is organized in parallel, with (D–F) displaying cocaine-induced NAc [glucose] changes vs. the same three parameters described above. R-values and linear regression are not shown for cocaine because of absence of correlation. Open circles with numbers are values for initial five time points (50 s) post-injection.
Mentions: Since changes in [glucose] are determined by changes in metabolic activity and vessel tone, next we examined the relationships between drug-induced glucose responses, NAc-Muscle and Skin-Muscle differentials, two indices that reflect intra-brain heat accumulation due to metabolic activation and the state of skin vessels, respectively; the analysis window in this case was defined from the moment of drug injection (0 s) to the peak effect of MDPV on NAc glucose (360 s) (Figure 7).

Bottom Line: Using enzyme-based glucose sensors coupled with amperometery in freely moving rats, we found that MDPV tonically decreases NAc glucose levels, a response that is opposite to what we previously observed with cocaine.By analyzing Skin-Muscle temperature differentials, a valid measure of skin vascular tone, we found that MDPV induces vasoconstriction; a similar effect at the level of cerebral vessels could be responsible for the MDPV-induced decrease in NAc glucose.While cocaine also induced comparable, if not slightly stronger peripheral vasoconstriction, this effect was overpowered by local neural activity-induced vasodilation, resulting in rapid surge in NAc glucose.

View Article: PubMed Central - PubMed

Affiliation: In-Vivo Electrophysiology Unit, Behavioral Neuroscience Branch, National Institute on Drug Abuse - Intramural Research Program, Department of Health and Human Services, National Institutes of Health Baltimore, MD, USA.

ABSTRACT
Methylenedioxypyrovalerone (MDPV) is generally considered to be a more potent cocaine-like psychostimulant, as it shares a similar pharmacological profile with cocaine and induces similar physiological and locomotor responses. Recently, we showed that intravenous cocaine induces rapid rise in nucleus accumbens (NAc) glucose and established its relation to neural activation triggered by the peripheral drug actions. This study was conducted to find out whether MDPV, at a behaviorally equivalent dose, shares a similar pattern of NAc glucose dynamics. Using enzyme-based glucose sensors coupled with amperometery in freely moving rats, we found that MDPV tonically decreases NAc glucose levels, a response that is opposite to what we previously observed with cocaine. By analyzing Skin-Muscle temperature differentials, a valid measure of skin vascular tone, we found that MDPV induces vasoconstriction; a similar effect at the level of cerebral vessels could be responsible for the MDPV-induced decrease in NAc glucose. While cocaine also induced comparable, if not slightly stronger peripheral vasoconstriction, this effect was overpowered by local neural activity-induced vasodilation, resulting in rapid surge in NAc glucose. These results imply that cocaine-users may be more susceptible to addiction than MDPV-users due to the presence of an interoceptive signal (i.e., sensory cue), which may result in earlier and more direct reward detection. Additionally, while health complications arising from acute cocaine use are typically cardiovascular related, MDPV may be more dangerous to the brain due to uncompensated cerebral vasoconstriction.

No MeSH data available.


Related in: MedlinePlus