Distinct Neurochemical Adaptations Within the Nucleus Accumbens Produced by a History of Self-Administered vs Non-Contingently Administered Intravenous Methamphetamine

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 37; no. 3; pp. 707 - 722
• Main Authors: LOMINAC, Kevin D, SACRAMENTO, Arianne D, SZUMLINSKI, Karen K, KIPPIN, Tod E
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.02.2012
• Subjects: Adaptations; Addictions; Animal cognition; Animals; Biological and medical sciences; Brain research; Central Nervous System Stimulants - administration & dosage; Data processing; Dopamine; Dopamine - metabolism; Drug abuse; Drug dosages; Drug withdrawal; Glutamic acid; Glutamic Acid - metabolism; Intravenous administration; Male; Medical sciences; Membrane Glycoproteins; Methamphetamine; Methamphetamine - administration & dosage; Microdialysis; Neurobiology; Neuropharmacology; Neurosciences; Neurotransmission; Nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Original; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychomotor stimulants; Psychopharmacology; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-1; Self Administration; Withdrawal; United States > US; Santa Barbara California; California; Amphetamine derivatives; Dopamine; Intravenous administration; CNS stimulant; Psychotropic; Central nervous system; Metamfetamine; Basal ganglion; Sympathomimetic; Self administration; Catecholamine; Glutamate; History; Encephalon; Nucleus accumbens; Addiction; methamphetamine; self-administration; Excitatory aminoacid; Neurotransmitter; Drug of abuse; Adaptation
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/npp.2011.248

Methamphetamine is a highly addictive psychomotor stimulant yet the neurobiological consequences of methamphetamine self-administration remain under-characterized. Thus, we employed microdialysis in rats trained to self-administer intravenous (IV) infusions of methamphetamine (METH-SA) or saline (SAL) and a group of rats receiving non-contingent IV infusions of methamphetamine (METH-NC) at 1 or 21 days withdrawal to determine the dopamine and glutamate responses in the nucleus accumbens (NAC) to a 2 mg/kg methamphetamine intraperitoneal challenge. Furthermore, basal NAC extracellular glutamate content was assessed employing no net-flux procedures in these three groups at both time points. At both 1- and 21-day withdrawal points, methamphetamine elicited a rise in extracellular dopamine in SAL animals and this effect was sensitized in METH-NC rats. However, METH-SA animals showed a much greater sensitized dopamine response to the drug challenge compared with the other groups. Additionally, acute methamphetamine decreased extracellular glutamate in both SAL and METH-NC animals at both time-points. In contrast, METH-SA rats exhibited a modest and delayed rise in glutamate at 1-day withdrawal and this rise was sensitized at 21 days withdrawal. Finally, no net-flux microdialysis revealed elevated basal glutamate and increased extraction fraction at both withdrawal time-points in METH-SA rats. Although METH-NC rats exhibited no change in the glutamate extraction fraction, they exhibited a time-dependent elevation in basal glutamate levels. These data illustrate for the first time that a history of methamphetamine self-administration produces enduring changes in NAC neurotransmission and that non-pharmacological factors have a critical role in the expression of these methamphetamine-induced neurochemical adaptations.