MDPV (3,4-methylenedioxypyrovalerone) is a synthetic cathinone illegally marketed as “bath salts” or “plant food” and consumed for its psychostimulant effects similar to those produced by cocaine, amphetamines and MDMA. Clinical reports indicate that MDPV produce euphoria, increase alertness and at high doses it causes agitation, psychosis, tachycardia and even death (1). In particular, the second leading cause of death induced by MDPV and other cathinones is associated with self-harm, risky and violent behavior (2, 3). Anecdotal reports suggests that MDPV increases violent aggressive behavior in men similar to that reported for alcohol and cocaine consumption (4). In rodents, MDPV reproduces the typical physiological effects of psychostimulant drugs, showing a greater potency compared to cocaine (5). Nevertheless, its role on aggressive behavior is still unknowns. Therefore, the aim of this study was to evaluate the effect of MDPV on aggressive behavior in mice and to compare its action with that induced by cocaine. The Resident-Intruder paradigm in isolated mice (6) was undertaken to investigate the effect of MDPV and cocaine on aggressive behavior. Saline administration causes an increase in aggressive behavior in 7% of total mice (n=50) with an increase of bite frequency of +52±1% respect to control baseline. Systemic MDPV administration (i.p.) at 0.1 and 10 mg/Kg causes an increased aggressive behavior in 46% and 55 % of total mice (n=50 for each treatment) with an increased frequency of bites of +134±22% and +155±18 % respectively. Similarly, cocaine administration (i.p.) at 0.1 and 10 mg/Kg causes an increased aggressive behavior in 13% and 27 % of total mice (n=50 for each treatment) with an increased frequency of bites of +82±8% and +132±11 % respectively, proving to be less potent than MDPV in inducing aggressive behavior in mice. The aggressive effect caused by MDPV is consistent with the positive modulation on catecholamine release (5) and its powerful action may reflect its stronger ability to inhibit dopamine and norepinephrine uptake respect to cocaine (5). These results show for the first time that MDPV enhance aggressive behavior in mice with grater potency compared to cocaine. This aspect should be carefully investigated for the prevention of interpersonal violence in human induced by novel psychoactive drug consumption. (1) Prosser J.M. and Nelson L.S. (2012) J Med Toxicol. 8: 33-42. (2) Marinetti L.J. and Antonides H.M. (2013) J. Anal. Toxicol. 37: 135-146. (3) Schifano F., Corkery J. and Ghodse A.H. (2012) J. Clin. Psychopharmacol. 32: 710-714. (4) Chermack S.T. and Blow F.C. (2002) Drug Alcohol Depend. 58: 43-54. (5) Baumann M.H., Partilla J.S., Lehener K.R. et al., (2013) Neuropsychopharmacology 38:552-562. (6) Miczec K.A. and O’Donnel J.M. (1978) Psychopharmacology 57: 47-55

Powerful cocaine-like action of MDPV on aggressive behaviour in isolated mice

MARTI, Matteo;
2013

Abstract

MDPV (3,4-methylenedioxypyrovalerone) is a synthetic cathinone illegally marketed as “bath salts” or “plant food” and consumed for its psychostimulant effects similar to those produced by cocaine, amphetamines and MDMA. Clinical reports indicate that MDPV produce euphoria, increase alertness and at high doses it causes agitation, psychosis, tachycardia and even death (1). In particular, the second leading cause of death induced by MDPV and other cathinones is associated with self-harm, risky and violent behavior (2, 3). Anecdotal reports suggests that MDPV increases violent aggressive behavior in men similar to that reported for alcohol and cocaine consumption (4). In rodents, MDPV reproduces the typical physiological effects of psychostimulant drugs, showing a greater potency compared to cocaine (5). Nevertheless, its role on aggressive behavior is still unknowns. Therefore, the aim of this study was to evaluate the effect of MDPV on aggressive behavior in mice and to compare its action with that induced by cocaine. The Resident-Intruder paradigm in isolated mice (6) was undertaken to investigate the effect of MDPV and cocaine on aggressive behavior. Saline administration causes an increase in aggressive behavior in 7% of total mice (n=50) with an increase of bite frequency of +52±1% respect to control baseline. Systemic MDPV administration (i.p.) at 0.1 and 10 mg/Kg causes an increased aggressive behavior in 46% and 55 % of total mice (n=50 for each treatment) with an increased frequency of bites of +134±22% and +155±18 % respectively. Similarly, cocaine administration (i.p.) at 0.1 and 10 mg/Kg causes an increased aggressive behavior in 13% and 27 % of total mice (n=50 for each treatment) with an increased frequency of bites of +82±8% and +132±11 % respectively, proving to be less potent than MDPV in inducing aggressive behavior in mice. The aggressive effect caused by MDPV is consistent with the positive modulation on catecholamine release (5) and its powerful action may reflect its stronger ability to inhibit dopamine and norepinephrine uptake respect to cocaine (5). These results show for the first time that MDPV enhance aggressive behavior in mice with grater potency compared to cocaine. This aspect should be carefully investigated for the prevention of interpersonal violence in human induced by novel psychoactive drug consumption. (1) Prosser J.M. and Nelson L.S. (2012) J Med Toxicol. 8: 33-42. (2) Marinetti L.J. and Antonides H.M. (2013) J. Anal. Toxicol. 37: 135-146. (3) Schifano F., Corkery J. and Ghodse A.H. (2012) J. Clin. Psychopharmacol. 32: 710-714. (4) Chermack S.T. and Blow F.C. (2002) Drug Alcohol Depend. 58: 43-54. (5) Baumann M.H., Partilla J.S., Lehener K.R. et al., (2013) Neuropsychopharmacology 38:552-562. (6) Miczec K.A. and O’Donnel J.M. (1978) Psychopharmacology 57: 47-55
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2089812
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