Sensitizing regimens of (+/-)3, 4-methylenedioxymethamphetamine (ecstasy) elicit enduring and differential structural alterations in the brain motive circuit of the rat.
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.
Ball
K T
KT
Department of Psychology, Bloomsburg University of Pennsylvania, 400 East Second Street, Bloomsburg, PA 17815-1301, USA.
Wellman
C L
CL
Fortenberry
E
E
Rebec
G V
GV
D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D054022:Cerebrum / Q000166:cytology / Q000187:drug effects*; D049229:Dendritic Spines / Q000187:drug effects*; D004334:Drug Administration Schedule; D006179:Gyrus Cinguli / Q000166:cytology / Q000187:drug effects; D006213:Hallucinogens / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage* / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects
D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine