Exposure to stress can profoundly affect the responsiveness to drugs of abuse in both experimental animals and humans. Self-administration studies in laboratory animals have shown that both physical and psychological stressors, facilitate the acquisition of drug self-administration, possibly by enhancing the reinforcing effects of drugs of abuse (1). Ethanol (EtOH) is after nicotine the most abused substance in the Western World. Recent data confirm the relationship between stress and EtOH abuse, and indicate that EtOH abuse usually occurs after exposure to stress (2). EtOH's positive motivational properties have been consistently related to its ability to activate the mesolimbic dopamine (DA) system, and new evidences show that acetaldehyde (ACD), the main metabolite of EtOH, may contribute to the reinforcing effects of EtOH trough its own rewarding properties (3,4,5,6). On these basis, we sought to study in vivo the effect of EtOH and ACD administration on the bioelectrical activity of mesoaccumbens DA neurons in ventral tegmental area (VTA) in control and stressed rats. Adult male Wistar rats (280-300 g) were exposed to 1 hour restraint stress, using a plexiglass restrainer. Thereafter subjects were anesthetized with urethane (1.3 g/kg, i.p.), the femoral vein was cannulated to allow administration of EtOH (250-1000 mg/kg) and ACD (5-20 mg/kg). Mesoaccumbens DA cells were studied using single unit extracellular recording, coupled with antidromic identification from the nucleus accumbens shell. Both EtOH and ACD in control animals, dose-dependently increased the firing rate of VTA DA cells. On the contrary, in stressed animals both EtOH and ACD effects on mesoaccumbal neuronal activity, were drastically reduced. Our result confirm that ACD by itself increases the firing of VTA DA neurons. Considering the role of DA mesolimbic system in regulating the motivational properties of abused drugs, these data suggest that stress may alter the effects of EtOH, by influencing DA neuronal activity. 1)Piazza PV, TIPS, 1998 2)Zimmermann U, Neuropsychopharmacology, 2003 3)Foddai M, Neuropsychopharmacology, 2004 4)Melis M,Eur.J.Neurosci., 2007 5)Enrico P,Drug Alcohol Depend., 2009 6)Peana AT,Alcohol Clin.Exp.Res., 2008

Restraint stress prevents acetaldehyde and ethanol-induced increase in dopaminergic neuronal activity in the VTA of the rat / M., Mereu; Diana, Marco; G., Muggironi; Peana, Alessandra Tiziana; D., Sirca; Enrico, Paolo; M., Foddai. - (2009).

Restraint stress prevents acetaldehyde and ethanol-induced increase in dopaminergic neuronal activity in the VTA of the rat

DIANA, Marco;PEANA, Alessandra Tiziana;ENRICO, Paolo;
2009-01-01

Abstract

Exposure to stress can profoundly affect the responsiveness to drugs of abuse in both experimental animals and humans. Self-administration studies in laboratory animals have shown that both physical and psychological stressors, facilitate the acquisition of drug self-administration, possibly by enhancing the reinforcing effects of drugs of abuse (1). Ethanol (EtOH) is after nicotine the most abused substance in the Western World. Recent data confirm the relationship between stress and EtOH abuse, and indicate that EtOH abuse usually occurs after exposure to stress (2). EtOH's positive motivational properties have been consistently related to its ability to activate the mesolimbic dopamine (DA) system, and new evidences show that acetaldehyde (ACD), the main metabolite of EtOH, may contribute to the reinforcing effects of EtOH trough its own rewarding properties (3,4,5,6). On these basis, we sought to study in vivo the effect of EtOH and ACD administration on the bioelectrical activity of mesoaccumbens DA neurons in ventral tegmental area (VTA) in control and stressed rats. Adult male Wistar rats (280-300 g) were exposed to 1 hour restraint stress, using a plexiglass restrainer. Thereafter subjects were anesthetized with urethane (1.3 g/kg, i.p.), the femoral vein was cannulated to allow administration of EtOH (250-1000 mg/kg) and ACD (5-20 mg/kg). Mesoaccumbens DA cells were studied using single unit extracellular recording, coupled with antidromic identification from the nucleus accumbens shell. Both EtOH and ACD in control animals, dose-dependently increased the firing rate of VTA DA cells. On the contrary, in stressed animals both EtOH and ACD effects on mesoaccumbal neuronal activity, were drastically reduced. Our result confirm that ACD by itself increases the firing of VTA DA neurons. Considering the role of DA mesolimbic system in regulating the motivational properties of abused drugs, these data suggest that stress may alter the effects of EtOH, by influencing DA neuronal activity. 1)Piazza PV, TIPS, 1998 2)Zimmermann U, Neuropsychopharmacology, 2003 3)Foddai M, Neuropsychopharmacology, 2004 4)Melis M,Eur.J.Neurosci., 2007 5)Enrico P,Drug Alcohol Depend., 2009 6)Peana AT,Alcohol Clin.Exp.Res., 2008
2009
Restraint stress prevents acetaldehyde and ethanol-induced increase in dopaminergic neuronal activity in the VTA of the rat / M., Mereu; Diana, Marco; G., Muggironi; Peana, Alessandra Tiziana; D., Sirca; Enrico, Paolo; M., Foddai. - (2009).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/55891
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