title: Cholecystokinin activates CCKB receptors to excite cells and depress EPSCs in the rat rostral nucleus accumbens in vitro.
abstract: The peptide cholecystokinin (CCK) is abundant in the rat nucleus accumbens (NAc). Although it is colocalized with dopamine (DA) in afferent terminals in this region, neurochemical and behavioural reports are equally divided as to whether CCK enhances or diminishes DA's actions in this nucleus. To better understand the role of this peptide in the physiology of the NAc, we examined the effects of CCK on excitatory synaptic transmission and tested whether these are dependent on DA and/or other neuromodulators. Using whole-cell recording in rat forebrain slices containing the NAc, we show that sulphated CCK octapeptide (CCK-8S), the endogenously active neuropeptide, consistently depolarized cells and depressed evoked excitatory postsynaptic currents (EPSCs) in the rostral NAc. It caused a reversible, dose-dependent decrease in evoked EPSC amplitude that was accompanied by an increase in the decay constant of the EPSC but with no apparent change in paired pulse ratio. It was mimicked by unsulphated CCK-8 (CCK-8US), a CCK(B) receptor-selective agonist, and blocked by LY225910, a CCK(B) receptor-selective antagonist. Both CCK-8S and CCK-8US induced an inward current with a reversal potential around -90 mV that was accompanied by an increase in input resistance and action potential firing. The CCK-8S-induced EPSC depression was slightly reduced in the presence of SCH23390 but not in the presence of sulpiride or 8-cyclopentyltheophylline. By contrast, it was completely blocked by CGP55845, a potent GABA(B) receptor-selective antagonist. These results indicate that CCK excites NAc cells directly while depressing evoked EPSCs indirectly, mainly through the release of GABA.
authors.affiliation: Department of Applied Therapeutics, Faculty of Pharmacy, Health Science Centre, Kuwait University, PO Box 24923, Safat 13110, Kuwait. kombian@hsc.kuniv.edu.kw
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Kombian
authors.forename: Kethireddy V V
authors.initials: KV
authors.lastname: Ananthalakshmi
authors.forename: Subramanian S
authors.initials: SS
authors.lastname: Parvathy
authors.forename: Wandikayi C
authors.initials: WC
authors.lastname: Matowe
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B / Q000378:metabolism* / Q000502:physiology; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: C090019:8-sulfocholecystokinin octapeptide; D043887:Receptor, Cholecystokinin B; D002766:Cholecystokinin; D012844:Sincalide