title: The neural substrates for the rewarding and dopamine-releasing effects of medial forebrain bundle stimulation have partially discrepant frequency responses.
abstract: Midbrain dopamine neurons have long been implicated in the rewarding effect produced by electrical brain stimulation of the medial forebrain bundle (MFB). These neurons are excited trans-synaptically, but their precise role in intracranial self-stimulation (ICSS) has yet to be determined. This study assessed the hypothesis that midbrain dopamine neurons are in series with the directly stimulated substrate for self-stimulation of the MFB and either perform spatio-temporal integration of synaptic input from directly activated MFB fibers or relay the results of such integration to efferent stages of the reward circuitry. Psychometric current-frequency trade-off functions were derived from ICSS performance, and chemometric trade-off functions were derived from stimulation-induced dopamine transients in the nucleus accumbens (NAc) shell, measured by means of fast-scan cyclic voltammetry. Whereas the psychometric functions decline monotonically over a broad range of pulse frequencies and level off only at high frequencies, the chemometric functions obtained with the same rats and electrodes are either U-shaped or level off at lower pulse frequencies. This discrepancy was observed when the dopamine transients were recorded in either anesthetized or awake subjects. The lack of correspondence between the psychometric and chemometric functions is inconsistent with the hypothesis that dopamine neurons projecting to the NAc shell constitute an entire series stage of the neural circuit subserving self-stimulation of the MFB.
authors.affiliation: Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, 7141 Sherbrooke Street West, SP-244, Montréal, Québec H4B 1R6, Canada. Electronic address: mpy_cossette@hotmail.com.
authors.forename: M-P
authors.initials: MP
authors.lastname: Cossette
authors.affiliation: Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, 7141 Sherbrooke Street West, SP-244, Montréal, Québec H4B 1R6, Canada. Electronic address: kent.conover@gmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Conover
authors.affiliation: Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, 7141 Sherbrooke Street West, SP-244, Montréal, Québec H4B 1R6, Canada. Electronic address: peter.shizgal@concordia.ca.
authors.forename: P
authors.initials: P
authors.lastname: Shizgal
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000502:physiology*; D055664:Electrochemical Techniques; D058542:Implantable Neurostimulators; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology*; D011594:Psychometrics; D020318:Rats, Long-Evans; D012201:Reward; D012653:Self Stimulation / Q000502:physiology*
chemical_list: D004298:Dopamine
keywords: Brain stimulation reward; Current-frequency trade-off; Fast-scan cyclic voltammetry; Medial forebrain bundle; Nucleus accumbens; Phasic dopamine release