The role of dopamine D3 receptors in MDMA-induced behavioral sensitization
Methylenedioxymethamphetamine (MDMA), a common recreational drug of abuse, possesses stimulant properties attributed to the dopaminergic system (Frederick and Paule, 1997). The repeated administration of MDMA to laboratory animals also results in an enhanced drug response, commonly referred to as behavioral sensitization, to certain behaviors. Studies in our laboratory suggest that down-regulation of dopamine D3 receptors in the nucleus accumbens may be involved in methamphetamine sensitization, another amphetamine analog. Dopamine D3 receptors are highly localized in the nucleus accumbens area and are thought to have an inhibitory effect on locomotor activity. Locomotor activity is often the parameter used to measure behavioral sensitization. For behavioral studies, mice received either physiological saline or 5.0 mg/kg of MDMA daily for seven days followed by a ten-day withdrawal period. On day 18 (18 days after the first MDMA injection) a 2.5 mg/kg challenge dose of MDMA was given and locomotor activity was measured. Additionally, co-administration of a dopamine D3 receptor agonist or antagonist with MDMA provides insight to the effects of D3 receptor activation or suppression upon MDMA-induced behaviors. Cyclic adenosine monophosphate (cAMP) assays of limbic tissues containing the dopamine D3 receptor-rich nucleus accumbens reveal changes to the functionality of second messenger events. Ribonuclease Protection Assays (RPAs) identify MDMA-induced changes in gene expression, and Western Blot Analysis reveals the consequences of MDMA exposure at the level of protein expression. ^
Corey D Jones,
"The role of dopamine D3 receptors in MDMA-induced behavioral sensitization"
ETD Collection for Tennessee State University.