title: CaV1.3channel blockade in the extended amygdala has a delayed effect on the reward efficacy of medial forebrain bundle stimulation.
abstract: Previous work in our laboratory has shown that stimulating D2 dopamine receptors in the central sublenticular extended amygdala (SLEAc) can render medial forebrain bundle (MFB) stimulation less rewarding. One of the many ways in which D2 stimulation could affect the activity status of SLEAc neurons is by indirectly blocking calcium ion (Ca2+) influx through CaV1.3channels. He we directly investigate the effects of blocking CaV1.3channels on the rewarding effect of MFB stimulation. In experiment one, CaV1.3blockade with the phenylalkylamine verapamil (2.5 and 5.0μg) or the benzothiazepine diltiazem (5.0 and 10.0μg) did not significantly decrease MFB stimulation's reward efficacy relative to injections of saline. However, there were indications of an unanticipated 24-h-delayed effect of the higher dose of diltiazem - injected ipsilateral to the stimulation site - on the stimulation pulse frequency required to maintain half-maximal response rates ("required frequency"). Experiment two focused on and tracked the time course of this effect. Injections of 10μg of diltiazem decreased required frequency significantly more than did saline injections 24h after injection but not immediately after injection. Required frequency values returned to baseline levels within 48h after injection. This time course is consistent with cellular processes that regulate the insertion of GABA-A receptors in neural membranes. GABA-A-mediated neural communication is implicated in maintaining basal forebrain medium spiny neurons in an excitable state. Therefore, these results may indicate that sustaining SLEAc neurons in an excitable state may be important for MFB stimulation to retain its rewarding properties.
authors.affiliation: Departments of Psychology and Biological Sciences, University of Wisconsin-Whitewater, 800 West, Main Street, Whitewater, WI, USA. Electronic address: waraczym@uww.edu.
authors.forename: Meg
authors.initials: M
authors.lastname: Waraczynski
authors.affiliation: Departments of Psychology and Biological Sciences, University of Wisconsin-Whitewater, 800 West, Main Street, Whitewater, WI, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Abbott
authors.affiliation: Departments of Psychology and Biological Sciences, University of Wisconsin-Whitewater, 800 West, Main Street, Whitewater, WI, USA.
authors.forename: Alex V
authors.initials: AV
authors.lastname: Schultz
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001703:Biophysics; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007839:Functional Laterality / Q000187:drug effects; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; C093712:Cacna1d protein, rat; D014700:Verapamil; D004110:Diltiazem
keywords: Brain stimulation reward; Calcium channel; Extended amygdala; Medial forebrain bundle