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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

Relative changes in NAc temperature (A,B), NAc-Muscle and Skin-Muscle differentials (D,E) and locomotion (H,I) induced by MDPV and cocaine injections (1–4). All parameters are shown with 1-min time resolution for 60 min post-injection. Right panels (C,F,G,J) shows differences in the effects of each drug depending upon injection number and evaluated as the area under the curve (AUC) for 45 min post-injection. For cocaine, One-Way RM ANOVA revealed significant effect on injection number on NAc temperature [F(3, 21) = 6.25, p < 0.05], Skin-Muscle differential [F(3, 21) = 4.07, p < 0.05] and locomotion [F(3, 21) = 4.42, p < 0.05]. For MDPV, the effect was significant only for locomotion [F(3, 21) = 3.15, p < 0.05].
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Figure 6: Relative changes in NAc temperature (A,B), NAc-Muscle and Skin-Muscle differentials (D,E) and locomotion (H,I) induced by MDPV and cocaine injections (1–4). All parameters are shown with 1-min time resolution for 60 min post-injection. Right panels (C,F,G,J) shows differences in the effects of each drug depending upon injection number and evaluated as the area under the curve (AUC) for 45 min post-injection. For cocaine, One-Way RM ANOVA revealed significant effect on injection number on NAc temperature [F(3, 21) = 6.25, p < 0.05], Skin-Muscle differential [F(3, 21) = 4.07, p < 0.05] and locomotion [F(3, 21) = 4.42, p < 0.05]. For MDPV, the effect was significant only for locomotion [F(3, 21) = 3.15, p < 0.05].

Mentions: When analyzed with respect to injection number, MDPV-induced increases in NAc temperature became larger with each subsequent injection (Figures 6B,C). This effect was evident with respect to response magnitude but the increase in the AUC did not reach statistical significance. Despite this apparent sensitization, both NAc-Muscle and Skin-Muscle differentials remained relatively constant for each subsequent injection (Figures 6E–G). A significant increase in locomotor activity [Figures 6I,J; F(3, 21) = 3.15, p < 0.05] was also detected across injections.


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)

Relative changes in NAc temperature (A,B), NAc-Muscle and Skin-Muscle differentials (D,E) and locomotion (H,I) induced by MDPV and cocaine injections (1–4). All parameters are shown with 1-min time resolution for 60 min post-injection. Right panels (C,F,G,J) shows differences in the effects of each drug depending upon injection number and evaluated as the area under the curve (AUC) for 45 min post-injection. For cocaine, One-Way RM ANOVA revealed significant effect on injection number on NAc temperature [F(3, 21) = 6.25, p < 0.05], Skin-Muscle differential [F(3, 21) = 4.07, p < 0.05] and locomotion [F(3, 21) = 4.42, p < 0.05]. For MDPV, the effect was significant only for locomotion [F(3, 21) = 3.15, p < 0.05].
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Figure 6: Relative changes in NAc temperature (A,B), NAc-Muscle and Skin-Muscle differentials (D,E) and locomotion (H,I) induced by MDPV and cocaine injections (1–4). All parameters are shown with 1-min time resolution for 60 min post-injection. Right panels (C,F,G,J) shows differences in the effects of each drug depending upon injection number and evaluated as the area under the curve (AUC) for 45 min post-injection. For cocaine, One-Way RM ANOVA revealed significant effect on injection number on NAc temperature [F(3, 21) = 6.25, p < 0.05], Skin-Muscle differential [F(3, 21) = 4.07, p < 0.05] and locomotion [F(3, 21) = 4.42, p < 0.05]. For MDPV, the effect was significant only for locomotion [F(3, 21) = 3.15, p < 0.05].
Mentions: When analyzed with respect to injection number, MDPV-induced increases in NAc temperature became larger with each subsequent injection (Figures 6B,C). This effect was evident with respect to response magnitude but the increase in the AUC did not reach statistical significance. Despite this apparent sensitization, both NAc-Muscle and Skin-Muscle differentials remained relatively constant for each subsequent injection (Figures 6E–G). A significant increase in locomotor activity [Figures 6I,J; F(3, 21) = 3.15, p < 0.05] was also detected across injections.

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