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Cck-8 injected into the nucleus accumbens attenuates the supersensitive locomotor response to apomorphine in 6-ohda and chronic-neuroleptic treated rats

Academic Article
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Overview

authors

  • Weiss, Friedbert
  • Ettenberg, A.
  • Koob, George

publication date

  • 1989

journal

  • Psychopharmacology  Journal

abstract

  • Postsynaptic dopamine-cholecystokinin (CCK) interactions in the nucleus accumbens were studied in two behavioral preparations of DA receptor supersensitivity: chronic-neuroleptic treated and 6-hydroxydopamine (6-OHDA) denervated rats. Subcutaneous (SC) injections of apomorphine (APO; 0.15 mg/kg) in experiment 1 produced marked hyperlocomotion in rats following 12 days of pretreatment with cis-[Z]-flupenthixol (2 mg/kg; twice per day). Bilateral intra-accumbens (N.Acc.) microinjections of CCK-8 (2 ng and 2 micrograms) reliably reduced APO-stimulated hyperlocomotion. An intermediate CCK dose (20 ng) was without effect. No change in APO responsivity following chronic vehicle treatment was observed and the baseline APO response was not altered by CCK at any dose. Denervation of mesolimbic dopamine (DA) terminals by intra-N.Acc. injections of 6-hydroxydopamine (6-OHDA; 8 micrograms/side) in experiment 2 similarly resulted in intense locomotor hyperactivity after APO stimulation (0.1 mg/kg; SC). Bilateral intra-N.Acc. injections of CCK-8 (1, 10, 100 ng, and 1 micrograms) significantly attenuated the supersensitive locomotor response to APO. As in experiment 1, CCK produced "biphasic" dose-response effects with strong attenuation that persisted throughout the entire 60-min test at both high (1 microgram) and low (1 ng) doses. Intermediate CCK doses (10 and 100 ng) produced only short-term reductions in activity. Hypomotility induced by APO in SHAM-lesioned rats was not effectively reversed by CCK treatments. CCK had no effect on unstimulated baseline locomotor activity in either 6-OHDA or SHAM-lesioned rats. These results provide further evidence that CCK-8 modulates mesolimbic DA activity by functionally opposing the postsynaptic effects of DA in the region of the nucleus accumbens.

subject areas

  • Animals
  • Antipsychotic Agents
  • Apomorphine
  • Brain Chemistry
  • Flupenthixol
  • Haloperidol
  • Hydroxydopamines
  • Injections
  • Male
  • Motor Activity
  • Nucleus Accumbens
  • Oxidopamine
  • Rats
  • Rats, Inbred Strains
  • Septal Nuclei
  • Sincalide
  • Sympathectomy, Chemical
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Identity

International Standard Serial Number (ISSN)

  • 0033-3158

Digital Object Identifier (DOI)

  • 10.1007/bf00445568

PubMed ID

  • 2574480
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Additional Document Info

start page

  • 409

end page

  • 415

volume

  • 99

issue

  • 3

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