Inhibition of neuronal nitric oxide synthase suppresses the maintenance but not the induction of psychomotor sensitization to MDMA ('Ecstasy') and p-chloroamphetamine in mice.
Karen L. Anderson, Yossef Itzhak
Nitric oxide : biology and chemistry August 2003 DOI: 10.1016/s1089-8603(03)00046-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Swiss Webster mice |
| Interventions | MDMA PCA 7-NI |
| Dose | MDMA 10 mg/kg, PCA 5 mg/kg, 7-NI 25 mg/kg |
| Duration | Six consecutive days of drug administration, with challenge injections later |
| Topics | MDMA |
| Key findings | 7-NI blocked the maintenance but not the induction or expression of psychomotor sensitization to MDMA and PCA in mice. MDMA and PCA did not produce conditioned hyperlocomotion. The authors argue that induction and expression involve serotonergic transmission independent of nNOS, while maintenance requires nNOS activity and dopaminergic transmission. |
Abstract
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 (10 mg/kg) and PCA (5 mg/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 (25 mg/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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 5
- Differential Response of nNOS Knockout Mice to MDMA (“Ecstasy”)‐ and Methamphetamine‐Induced Psychomotor Sensitization and Neurotoxicity Annals of the New York Academy of Sciences October 1, 2004
- MDMA and memory, addiction, and depression: dose-effect analysis Psychopharmacology March 1, 2022
- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
- Role of nitric oxide pathway in the conditioned rewarding effects of MDMA in mice. Behavioural Brain Research May 4, 2017
- Effects of group exposure on single injection-induced behavioral sensitization to drugs of abuse in mice. Drug and Alcohol Dependence November 1, 2011
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