TY - JOUR
T1 - Inhibition of neuronal nitric oxide synthase suppresses the maintenance but not the induction of psychomotor sensitization to MDMA ('Ecstasy') and p-chloroamphetamine in mice
AU - Anderson, Karen L.
AU - Itzhak, Yossef
N1 - Funding Information:
This work was supported by USPHS award DA 12867 from the National Institute on Drug Abuse, USA.
PY - 2003/8
Y1 - 2003/8
N2 - Repeated exposure to psychostimulants such as cocaine and amphetamines results in behavioral sensitization, a paradigm thought to be relevant to drug craving and addiction in humans. We have previously shown that the induction, expression, and maintenance of psychomotor sensitization to cocaine, methamphetamine, and methylphenidate (indirect dopamine agonists) are blocked by co-administration of the neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI). In the present study, we investigated the effects of 7-NI on the induction, expression, and maintenance of psychomotor sensitization to 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') and p-chloroamphetamine (PCA). The following observations are reported: (a) Repeated administration of MDMA (10mg/kg) and PCA (5mg/kg) to Swiss Webster mice for six consecutive days caused a 3-fold increase in the psychomotor stimulating effect of the drugs on day 6 compared to day 1. (b) Pretreatment with 7-NI (25mg/kg) did not affect the induction and expression of sensitization to MDMA and PCA. (c) Pretreatment with 7-NI did, however, suppress the enduring sensitized response to challenge injections of MDMA and PCA which was observed in mice pretreated with vehicle instead of 7-NI. (d) Unlike other psychostimulants, MDMA and PCA treatment did not produce conditioned (context-dependent) hyperlocomotion. These findings, coupled with our previous studies, suggest the following: (a) The induction and expression of psychomotor sensitization to MDMA and PCA are independent of nNOS activity and involve primarily serotonergic transmission. (b) The maintenance of psychomotor sensitization is dependent on intact nNOS activity and involves primarily dopaminergic transmission.
AB - Repeated exposure to psychostimulants such as cocaine and amphetamines results in behavioral sensitization, a paradigm thought to be relevant to drug craving and addiction in humans. We have previously shown that the induction, expression, and maintenance of psychomotor sensitization to cocaine, methamphetamine, and methylphenidate (indirect dopamine agonists) are blocked by co-administration of the neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI). In the present study, we investigated the effects of 7-NI on the induction, expression, and maintenance of psychomotor sensitization to 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') and p-chloroamphetamine (PCA). The following observations are reported: (a) Repeated administration of MDMA (10mg/kg) and PCA (5mg/kg) to Swiss Webster mice for six consecutive days caused a 3-fold increase in the psychomotor stimulating effect of the drugs on day 6 compared to day 1. (b) Pretreatment with 7-NI (25mg/kg) did not affect the induction and expression of sensitization to MDMA and PCA. (c) Pretreatment with 7-NI did, however, suppress the enduring sensitized response to challenge injections of MDMA and PCA which was observed in mice pretreated with vehicle instead of 7-NI. (d) Unlike other psychostimulants, MDMA and PCA treatment did not produce conditioned (context-dependent) hyperlocomotion. These findings, coupled with our previous studies, suggest the following: (a) The induction and expression of psychomotor sensitization to MDMA and PCA are independent of nNOS activity and involve primarily serotonergic transmission. (b) The maintenance of psychomotor sensitization is dependent on intact nNOS activity and involves primarily dopaminergic transmission.
KW - Cocaine
KW - Condition locomotion
KW - Hyperlocomotion
KW - Methamphetamine
KW - Methylphenidate
KW - Psychostimulants
KW - Sensitization
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U2 - 10.1016/S1089-8603(03)00046-6
DO - 10.1016/S1089-8603(03)00046-6
M3 - Article
C2 - 14559429
AN - SCOPUS:0141996266
VL - 9
SP - 24
EP - 32
JO - Nitric Oxide - Biology and Chemistry
JF - Nitric Oxide - Biology and Chemistry
SN - 1089-8603
IS - 1
ER -