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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

Overall changes in temperature and locomotion induced by iv MDPV and cocaine. (A,B), mean ± SEM changes in absolute temperature recorded from the NAc, temporal muscle and skin. (C,D), relative temperature changes in the same locations. (F,G), changes in NAc-Muscle and Skin-Muscle temperature differentials. (I,J), overall changes in locomotion. Data were obtained from eight rats (32 injections of each drug). Right panels show between-drug differences in the effects on brain temperature (E), NAc-Muscle and Skin-Muscle differentials (H), and locomotion (K) as assessed by the area under the curve for 45 min post-injection. Asterisk shows significant between drug differences for skin temperature (p < 0.05).
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Figure 4: Overall changes in temperature and locomotion induced by iv MDPV and cocaine. (A,B), mean ± SEM changes in absolute temperature recorded from the NAc, temporal muscle and skin. (C,D), relative temperature changes in the same locations. (F,G), changes in NAc-Muscle and Skin-Muscle temperature differentials. (I,J), overall changes in locomotion. Data were obtained from eight rats (32 injections of each drug). Right panels show between-drug differences in the effects on brain temperature (E), NAc-Muscle and Skin-Muscle differentials (H), and locomotion (K) as assessed by the area under the curve for 45 min post-injection. Asterisk shows significant between drug differences for skin temperature (p < 0.05).

Mentions: As shown in Figure 4, MDPV and cocaine induced similar temperature responses: NAc and muscle temperatures modestly increased for ~40 min, while skin temperature rapidly decreased, slowly returning to baseline at ~30–40 min (Figures 4A–D). Brain and muscle temperature increases evaluated by AUC for 45-min post-injection were slightly higher for MDPV than cocaine, but the difference was not significant. However, decreases in skin temperature induced by MDPV were significantly weaker than that for cocaine (Figure 4E).


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)

Overall changes in temperature and locomotion induced by iv MDPV and cocaine. (A,B), mean ± SEM changes in absolute temperature recorded from the NAc, temporal muscle and skin. (C,D), relative temperature changes in the same locations. (F,G), changes in NAc-Muscle and Skin-Muscle temperature differentials. (I,J), overall changes in locomotion. Data were obtained from eight rats (32 injections of each drug). Right panels show between-drug differences in the effects on brain temperature (E), NAc-Muscle and Skin-Muscle differentials (H), and locomotion (K) as assessed by the area under the curve for 45 min post-injection. Asterisk shows significant between drug differences for skin temperature (p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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Figure 4: Overall changes in temperature and locomotion induced by iv MDPV and cocaine. (A,B), mean ± SEM changes in absolute temperature recorded from the NAc, temporal muscle and skin. (C,D), relative temperature changes in the same locations. (F,G), changes in NAc-Muscle and Skin-Muscle temperature differentials. (I,J), overall changes in locomotion. Data were obtained from eight rats (32 injections of each drug). Right panels show between-drug differences in the effects on brain temperature (E), NAc-Muscle and Skin-Muscle differentials (H), and locomotion (K) as assessed by the area under the curve for 45 min post-injection. Asterisk shows significant between drug differences for skin temperature (p < 0.05).
Mentions: As shown in Figure 4, MDPV and cocaine induced similar temperature responses: NAc and muscle temperatures modestly increased for ~40 min, while skin temperature rapidly decreased, slowly returning to baseline at ~30–40 min (Figures 4A–D). Brain and muscle temperature increases evaluated by AUC for 45-min post-injection were slightly higher for MDPV than cocaine, but the difference was not significant. However, decreases in skin temperature induced by MDPV were significantly weaker than that for cocaine (Figure 4E).

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