title: Intermittent bilateral deep brain stimulation of the nucleus accumbens shell reduces intravenous methamphetamine intake and seeking in Wistar rats.
abstract: OBJECTIVE There is increasing interest in neuromodulation for addiction. Methamphetamine abuse is a global health epidemic with no proven treatment. The objective of this study was to examine the effects of intermittent nucleus accumbens shell (AcbSh) deep brain stimulation (DBS) on operant methamphetamine intake and on methamphetamine seeking when stimulation is delivered in an environment different from that of drug use. METHODS Eighteen rats were implanted with intravenous (IV) catheters and bilateral AcbSh electrodes and subsequently underwent daily sessions in 2-lever (active/methamphetamine and inactive/no reward) operant chambers to establish IV methamphetamine self-administration. After stable responding was achieved, 3 hours of DBS or sham treatment was administered (sham: 0 µA, n = 8; active: 200 µA, n = 10) in a separate nondrug environment prior to the daily operant sessions for 5 consecutive days. Immediately following each DBS/sham treatment, rats were placed in the operant chambers to examine the effects of remote stimulation on methamphetamine intake. After the 5 days of therapy were finished, rats reestablished a posttreatment baseline, followed by extinction training, abstinence, and 1 day of relapse testing to assess methamphetamine-seeking behavior. RESULTS There was a decrease in total methamphetamine intake in rats receiving active DBS versus sham on Days 1 (42%) and 2 (44%). Methamphetamine administration returned to baseline levels following the cessation of DBS therapy. Compared with baseline drug responding, methamphetamine seeking was reduced (57%) in the DBS group but not in the sham group. CONCLUSIONS It is feasible to deliver noncontinuous DBS outside of the drug use environment with a resultant decrease in IV methamphetamine intake and seeking. The AcbSh is a neuroanatomical substrate for psychostimulant reinforcement and may be a target for intermittent neuromodulatory therapies that could be administered during brief periods of sobriety.
authors.affiliation: Department of Neurosurgery and.
authors.forename: Vinita
authors.initials: V
authors.lastname: Batra
authors.affiliation: Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
authors.forename: Thanh Lam N
authors.initials: TL
authors.lastname: Tran
authors.affiliation: Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
authors.forename: Jessica
authors.initials: J
authors.lastname: Caputo
authors.affiliation: Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
authors.forename: Glenn F
authors.initials: GF
authors.lastname: Guerin
authors.affiliation: Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Goeders
authors.affiliation: Department of Neurosurgery and.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wilden
mesh_terms: D061605:Administration, Intravenous; D019969:Amphetamine-Related Disorders / Q000503:physiopathology* / Q000628:therapy*; D000818:Animals; D002408:Catheters, Indwelling; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000502:physiology; D046690:Deep Brain Stimulation / Q000379:methods; D004195:Disease Models, Animal; D058999:Drug-Seeking Behavior / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage; D009714:Nucleus Accumbens / Q000503:physiopathology*; D017208:Rats, Wistar; D012646:Self Administration
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine
keywords: Acb = nucleus accumbens; AcbSh = nucleus accumbens shell; D1R = D1-receptor; DBS = beep brain stimulation; FR1 = fixed ratio of one; GABA = γ-aminobutyric acid; HFS = high-frequency stimulation; IV = intravenous; LFS = low-frequency stimulation; MSN = medium spiny neuron; PFC = prefrontal cortex; PSR = Pavlovian spontaneous recovery; TMS = transcranial magnetic stimulation; VTA = ventral tegmental area; deep brain stimulation; intravenous self-administration; methamphetamine; neuromodulation; relapse; substance addiction