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Sensitizing regimens of (+/-)3, 4-methylenedioxymethamphetamine (ecstasy) elicit enduring and differential structural alterations in the brain motive circuit of the rat.
Neuroscience. 2009 May 05; 160(2):264-74.N

Abstract

Repeated, intermittent exposure to the psychomotor stimulants amphetamine and cocaine induces a progressive and enduring augmentation of their locomotor-activating effects, known as behavioral sensitization, which is accompanied by similarly stable adaptations in the dendritic structure of cortico-striatal neurons. We examined whether repeated exposure to the increasingly abused amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) also results in long-lasting behavioral and morphological changes in mesocortical (medial prefrontal cortex) and ventral striatal (nucleus accumbens) neurons. Rats received two daily injections of either 5.0 mg/kg (+/-)-MDMA or saline vehicle, approximately 6 h apart, for 3 consecutive days, followed by 4 drug-free days for a total of 3 weeks. Following a 4-week drug-free period, MDMA-pretreated rats displayed behavioral sensitization, as well as large increases in spine density and the number of multiple-headed spines on medium spiny neurons in core and shell subregions of nucleus accumbens. In medial prefrontal cortex, the prelimbic subregion showed increased spine density on distal dendrites of layer V pyramidal neurons, while the anterior cingulate subregion showed a change in the distribution of dendritic material instead. Collectively, our results show that long-lasting locomotor sensitization to MDMA is accompanied by reorganization of synaptic connectivity in limbic-cortico-striatal circuitry. The differential plasticity in cortical subregions, moreover, suggests that drug-induced structural changes are not homogeneous and may be specific to the circuitry underlying long-term changes in drug-seeking and drug-taking behavior.

Authors+Show Affiliations

Department of Psychology, Bloomsburg University of Pennsylvania, 400 East Second Street, Bloomsburg, PA 17815-1301, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19236907

Citation

Ball, K T., et al. "Sensitizing Regimens of (+/-)3, 4-methylenedioxymethamphetamine (ecstasy) Elicit Enduring and Differential Structural Alterations in the Brain Motive Circuit of the Rat." Neuroscience, vol. 160, no. 2, 2009, pp. 264-74.
Ball KT, Wellman CL, Fortenberry E, et al. Sensitizing regimens of (+/-)3, 4-methylenedioxymethamphetamine (ecstasy) elicit enduring and differential structural alterations in the brain motive circuit of the rat. Neuroscience. 2009;160(2):264-74.
Ball, K. T., Wellman, C. L., Fortenberry, E., & Rebec, G. V. (2009). Sensitizing regimens of (+/-)3, 4-methylenedioxymethamphetamine (ecstasy) elicit enduring and differential structural alterations in the brain motive circuit of the rat. Neuroscience, 160(2), 264-74. https://doi.org/10.1016/j.neuroscience.2009.02.025
Ball KT, et al. Sensitizing Regimens of (+/-)3, 4-methylenedioxymethamphetamine (ecstasy) Elicit Enduring and Differential Structural Alterations in the Brain Motive Circuit of the Rat. Neuroscience. 2009 May 5;160(2):264-74. PubMed PMID: 19236907.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sensitizing regimens of (+/-)3, 4-methylenedioxymethamphetamine (ecstasy) elicit enduring and differential structural alterations in the brain motive circuit of the rat. AU - Ball,K T, AU - Wellman,C L, AU - Fortenberry,E, AU - Rebec,G V, Y1 - 2009/02/21/ PY - 2008/12/11/received PY - 2009/02/05/revised PY - 2009/02/07/accepted PY - 2009/2/25/entrez PY - 2009/2/25/pubmed PY - 2009/10/22/medline SP - 264 EP - 74 JF - Neuroscience JO - Neuroscience VL - 160 IS - 2 N2 - Repeated, intermittent exposure to the psychomotor stimulants amphetamine and cocaine induces a progressive and enduring augmentation of their locomotor-activating effects, known as behavioral sensitization, which is accompanied by similarly stable adaptations in the dendritic structure of cortico-striatal neurons. We examined whether repeated exposure to the increasingly abused amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) also results in long-lasting behavioral and morphological changes in mesocortical (medial prefrontal cortex) and ventral striatal (nucleus accumbens) neurons. Rats received two daily injections of either 5.0 mg/kg (+/-)-MDMA or saline vehicle, approximately 6 h apart, for 3 consecutive days, followed by 4 drug-free days for a total of 3 weeks. Following a 4-week drug-free period, MDMA-pretreated rats displayed behavioral sensitization, as well as large increases in spine density and the number of multiple-headed spines on medium spiny neurons in core and shell subregions of nucleus accumbens. In medial prefrontal cortex, the prelimbic subregion showed increased spine density on distal dendrites of layer V pyramidal neurons, while the anterior cingulate subregion showed a change in the distribution of dendritic material instead. Collectively, our results show that long-lasting locomotor sensitization to MDMA is accompanied by reorganization of synaptic connectivity in limbic-cortico-striatal circuitry. The differential plasticity in cortical subregions, moreover, suggests that drug-induced structural changes are not homogeneous and may be specific to the circuitry underlying long-term changes in drug-seeking and drug-taking behavior. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/19236907/Sensitizing_regimens_of__+/__3_4_methylenedioxymethamphetamine__ecstasy__elicit_enduring_and_differential_structural_alterations_in_the_brain_motive_circuit_of_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(09)00193-6 DB - PRIME DP - Unbound Medicine ER -