Effects of administration of cholecystokinin into the VTA on DA overflow in nucleus accumbens and amygdala of freely moving rats.
The carboxyterminal octapeptide of cholecystokinin (CCK-8) coexists with dopamine (DA) in mesolimbic neurons of the ventral tegmental area (VTA). In the present study, in vivo microdialysis in freely moving rats was used to assess the relative effects of sulfated CCK-8 (CCK-8S), unsulfated CCK-8 (CCK-8US) and CCK tetrapeptide (CCK-4), focally injected into the VTA, on DA overflow in two mesolimbic DA/CCK-8S terminal regions, the nucleus accumbens and the amygdala. Consistent with electrophysiological findings, microinjection of CCK-8S, but not CCK-8US or CCK-4, elicited increases in DA overflow in both terminal regions. In the absence of anatomical evidence of CCK-containing fibers in the VTA region, it seems reasonable to conclude that the modulation of terminal DA overflow by CCK-8S through actions at the somatodendritic region represents a form of autoregulation of these cells. Whereas CCK-8US and CCK-4 are preferential CCK-B receptor agonists, CCK-8S binds non-selectively to CCK-A and CCK-B receptors. Thus, these results implicate CCK-A receptors in the stimulatory effects of CCK-8S on VTA DA neurons.
Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
M E
ME
Hamilton
A S
AS
Freeman
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D006706:Homeostasis; D007478:Iontophoresis; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D009068:Movement; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects*
D015259:Dopamine Agents; D002766:Cholecystokinin