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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.


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High-resolution analysis of changes in temperature and locomotion induced by MDPV and cocaine. (A), mean ± SEM changes in NAc temperature. Two-Way RM ANOVA revealed a significant of Time [F(49, 1519) = 80.05, p < 0.001] and Drug × Time Interaction [F(49, 1519) = 4.12] with no effect of Drug [F(1, 31) = 3.16, p = 0.08]. Small arrow with asterisk shows the moment (~160 s) when two curves significantly diverge from each other. (B) shows mean ± SEM changes in NAc-Muscle and Skin-Muscle differentials. Two-Way RM ANOVA revealed a main effect of Drug [F(1, 31) = 4.32, p < 0.05], Time [F(49, 1519) = 54.45, p < 0.01], and Drug × Time Interaction [F(49, 1519) = 1.77, p < 0.01] on Skin-Muscle differential, with no significant changes for NAc-Muscle differential. (C), mean ± SEM changes in locomotion. The between-drug difference for locomotion was significant only for 210 s after the injection onset [Drug × Time interaction F(22, 682) = 1.57, p = 0.047]. Filled symbols in each graph show values significantly different from baseline revaluated by One-Way RM ANOVA.
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Figure 5: High-resolution analysis of changes in temperature and locomotion induced by MDPV and cocaine. (A), mean ± SEM changes in NAc temperature. Two-Way RM ANOVA revealed a significant of Time [F(49, 1519) = 80.05, p < 0.001] and Drug × Time Interaction [F(49, 1519) = 4.12] with no effect of Drug [F(1, 31) = 3.16, p = 0.08]. Small arrow with asterisk shows the moment (~160 s) when two curves significantly diverge from each other. (B) shows mean ± SEM changes in NAc-Muscle and Skin-Muscle differentials. Two-Way RM ANOVA revealed a main effect of Drug [F(1, 31) = 4.32, p < 0.05], Time [F(49, 1519) = 54.45, p < 0.01], and Drug × Time Interaction [F(49, 1519) = 1.77, p < 0.01] on Skin-Muscle differential, with no significant changes for NAc-Muscle differential. (C), mean ± SEM changes in locomotion. The between-drug difference for locomotion was significant only for 210 s after the injection onset [Drug × Time interaction F(22, 682) = 1.57, p = 0.047]. Filled symbols in each graph show values significantly different from baseline revaluated by One-Way RM ANOVA.

Mentions: When analyzed at a high time-resolution (10-s bins), MDPV displayed more rapid and stronger effects on NAc temperatures than cocaine [Time × Drug interaction F(49, 1519) = 4.12, p < 0.05 (Figure 5A)]. Cocaine-induced NAc increase became significant at ~45 s, whereas MDPV-induced NAc increase became significant at 75 s from injection onset. The difference between curves became significantly different at ~140 s (see asterisk in Figure 5A). Both drugs had virtually identical effects on NAc-Muscle differentials, but the increase induced by cocaine had shorter rapid onset latency (15 vs. 45 s). Cocaine also displayed a significantly stronger effect on the Skin-Muscle differential [Drug F(1, 31) = 4.32, Drug × Time interaction F(49, 1519) = 1.77; both p < 0.05] (Figure 5B). The difference between curves became significant at ~50 s, and cocaine showed a much steeper, sharper drop in Skin-Muscle differential than MDPV.


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)

High-resolution analysis of changes in temperature and locomotion induced by MDPV and cocaine. (A), mean ± SEM changes in NAc temperature. Two-Way RM ANOVA revealed a significant of Time [F(49, 1519) = 80.05, p < 0.001] and Drug × Time Interaction [F(49, 1519) = 4.12] with no effect of Drug [F(1, 31) = 3.16, p = 0.08]. Small arrow with asterisk shows the moment (~160 s) when two curves significantly diverge from each other. (B) shows mean ± SEM changes in NAc-Muscle and Skin-Muscle differentials. Two-Way RM ANOVA revealed a main effect of Drug [F(1, 31) = 4.32, p < 0.05], Time [F(49, 1519) = 54.45, p < 0.01], and Drug × Time Interaction [F(49, 1519) = 1.77, p < 0.01] on Skin-Muscle differential, with no significant changes for NAc-Muscle differential. (C), mean ± SEM changes in locomotion. The between-drug difference for locomotion was significant only for 210 s after the injection onset [Drug × Time interaction F(22, 682) = 1.57, p = 0.047]. Filled symbols in each graph show values significantly different from baseline revaluated by One-Way RM ANOVA.
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Figure 5: High-resolution analysis of changes in temperature and locomotion induced by MDPV and cocaine. (A), mean ± SEM changes in NAc temperature. Two-Way RM ANOVA revealed a significant of Time [F(49, 1519) = 80.05, p < 0.001] and Drug × Time Interaction [F(49, 1519) = 4.12] with no effect of Drug [F(1, 31) = 3.16, p = 0.08]. Small arrow with asterisk shows the moment (~160 s) when two curves significantly diverge from each other. (B) shows mean ± SEM changes in NAc-Muscle and Skin-Muscle differentials. Two-Way RM ANOVA revealed a main effect of Drug [F(1, 31) = 4.32, p < 0.05], Time [F(49, 1519) = 54.45, p < 0.01], and Drug × Time Interaction [F(49, 1519) = 1.77, p < 0.01] on Skin-Muscle differential, with no significant changes for NAc-Muscle differential. (C), mean ± SEM changes in locomotion. The between-drug difference for locomotion was significant only for 210 s after the injection onset [Drug × Time interaction F(22, 682) = 1.57, p = 0.047]. Filled symbols in each graph show values significantly different from baseline revaluated by One-Way RM ANOVA.
Mentions: When analyzed at a high time-resolution (10-s bins), MDPV displayed more rapid and stronger effects on NAc temperatures than cocaine [Time × Drug interaction F(49, 1519) = 4.12, p < 0.05 (Figure 5A)]. Cocaine-induced NAc increase became significant at ~45 s, whereas MDPV-induced NAc increase became significant at 75 s from injection onset. The difference between curves became significantly different at ~140 s (see asterisk in Figure 5A). Both drugs had virtually identical effects on NAc-Muscle differentials, but the increase induced by cocaine had shorter rapid onset latency (15 vs. 45 s). Cocaine also displayed a significantly stronger effect on the Skin-Muscle differential [Drug F(1, 31) = 4.32, Drug × Time interaction F(49, 1519) = 1.77; both p < 0.05] (Figure 5B). The difference between curves became significant at ~50 s, and cocaine showed a much steeper, sharper drop in Skin-Muscle differential than MDPV.

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