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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 NAc [glucose] induced by intravenous MDPV and cocaine. (A), the mean (±SEM) change in currents recorded by glucose (red) and glucose- (blue) sensors shown in 1-min bins from 5 min before to 60 min after MDPV injections. (B), the mean ± SEM changes in NAc [glucose] induced by MDPV and cocaine. (C), the overall locomotor response to MDPV (green) and cocaine (black line). n, the number of drug injections and number of rats averaged for this analyses. Filled symbols in (B) show values significantly different from baseline (p < 0.05; Fisher post-hoc test after significant drug effect detected by One-Way RM ANOVA). Asterisk in (B) denotes the interval where there were significant differences between drugs detected by a Fisher post-hoc test after significant main effects of drug and Drug x Time interactions were found by Two-Way RM ANOVA.
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Figure 1: Overall changes in NAc [glucose] induced by intravenous MDPV and cocaine. (A), the mean (±SEM) change in currents recorded by glucose (red) and glucose- (blue) sensors shown in 1-min bins from 5 min before to 60 min after MDPV injections. (B), the mean ± SEM changes in NAc [glucose] induced by MDPV and cocaine. (C), the overall locomotor response to MDPV (green) and cocaine (black line). n, the number of drug injections and number of rats averaged for this analyses. Filled symbols in (B) show values significantly different from baseline (p < 0.05; Fisher post-hoc test after significant drug effect detected by One-Way RM ANOVA). Asterisk in (B) denotes the interval where there were significant differences between drugs detected by a Fisher post-hoc test after significant main effects of drug and Drug x Time interactions were found by Two-Way RM ANOVA.

Mentions: Initially we combined all MDPV-induced glucose responses independent of their injection number within the session and analyzed them at a 1-min resolution for 60 min post-injection (Figure 1). In contrast to a weak, not-significant increase followed by a slow decrease below baseline detected by glucose- sensors (blue line), currents detected by the glucose sensors (red line) rapidly decreased after the MDPV injection, but began to rebound from ~5 min post-injection exceeding the values detected by sensor (Figure 1A). By subtracting values detected by glucose and glucose- sensors, we found that glucose levels modestly but significantly decreased (~25 μM, nadir ~4 min) and then rebounded to levels slightly higher than the pre-injection baseline from ~20 min post-injection [F(31, 1740) = 5.51, p < 0.001; Figure 1B]. These changes contrasted to those induced by cocaine, which elicited a strong, bimodal increase in glucose (~60 μM, peak ~14 min) for ~45 min post-injection [F(27, 1620) = 15.35, p < 0.001; Figure 1B). As such, MDPV and cocaine induce opposite changes in NAc glucose [Two-Way ANOVA: main effect F(1, 56) = 7.21, Drug × Time interaction F(60, 3360) = 10.73; both p < 0.001], which differ in both the latency and duration. However, both MDPV and cocaine similarly increased locomotion for ~40 min post-injection, with no between-drug differences within the entire analysis interval (Figure 1C).


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 NAc [glucose] induced by intravenous MDPV and cocaine. (A), the mean (±SEM) change in currents recorded by glucose (red) and glucose- (blue) sensors shown in 1-min bins from 5 min before to 60 min after MDPV injections. (B), the mean ± SEM changes in NAc [glucose] induced by MDPV and cocaine. (C), the overall locomotor response to MDPV (green) and cocaine (black line). n, the number of drug injections and number of rats averaged for this analyses. Filled symbols in (B) show values significantly different from baseline (p < 0.05; Fisher post-hoc test after significant drug effect detected by One-Way RM ANOVA). Asterisk in (B) denotes the interval where there were significant differences between drugs detected by a Fisher post-hoc test after significant main effects of drug and Drug x Time interactions were found by Two-Way RM ANOVA.
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Related In: Results  -  Collection

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Figure 1: Overall changes in NAc [glucose] induced by intravenous MDPV and cocaine. (A), the mean (±SEM) change in currents recorded by glucose (red) and glucose- (blue) sensors shown in 1-min bins from 5 min before to 60 min after MDPV injections. (B), the mean ± SEM changes in NAc [glucose] induced by MDPV and cocaine. (C), the overall locomotor response to MDPV (green) and cocaine (black line). n, the number of drug injections and number of rats averaged for this analyses. Filled symbols in (B) show values significantly different from baseline (p < 0.05; Fisher post-hoc test after significant drug effect detected by One-Way RM ANOVA). Asterisk in (B) denotes the interval where there were significant differences between drugs detected by a Fisher post-hoc test after significant main effects of drug and Drug x Time interactions were found by Two-Way RM ANOVA.
Mentions: Initially we combined all MDPV-induced glucose responses independent of their injection number within the session and analyzed them at a 1-min resolution for 60 min post-injection (Figure 1). In contrast to a weak, not-significant increase followed by a slow decrease below baseline detected by glucose- sensors (blue line), currents detected by the glucose sensors (red line) rapidly decreased after the MDPV injection, but began to rebound from ~5 min post-injection exceeding the values detected by sensor (Figure 1A). By subtracting values detected by glucose and glucose- sensors, we found that glucose levels modestly but significantly decreased (~25 μM, nadir ~4 min) and then rebounded to levels slightly higher than the pre-injection baseline from ~20 min post-injection [F(31, 1740) = 5.51, p < 0.001; Figure 1B]. These changes contrasted to those induced by cocaine, which elicited a strong, bimodal increase in glucose (~60 μM, peak ~14 min) for ~45 min post-injection [F(27, 1620) = 15.35, p < 0.001; Figure 1B). As such, MDPV and cocaine induce opposite changes in NAc glucose [Two-Way ANOVA: main effect F(1, 56) = 7.21, Drug × Time interaction F(60, 3360) = 10.73; both p < 0.001], which differ in both the latency and duration. However, both MDPV and cocaine similarly increased locomotion for ~40 min post-injection, with no between-drug differences within the entire analysis interval (Figure 1C).

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