caa a22 4500 469078367 CHVBK 20180323132942.0 cr unu---uuuuu 170328e19921001xx s 000 0 eng 10.1007/BF00171085 doi (NATIONALLICENCE)springer-10.1007/BF00171085 Changes in cholecystokinin receptor binding in rat brain after selective damage of locus coeruleus projections by DSP 4 treatment [Elektronische Daten] [Jaanus Harro, Sukhwinder Jossan, Lars Oreland] Summary: Brain cholecystokinin (CCK)- and noradrenergic activities are two neurochemical systems implicated in anxiety and deficits in novelty-related behaviour. In order to clarify a possible interaction between CCK- and noradrenergic neurotransmission in the brain, DSP-4 [N(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a neurotoxin that selectively destroys noradrenaline-containing nerve terminals originating from the locus coeruleus, was administered to rats IP (10 and 50 mg/kg) seven days before decapitation. Noradrenaline uptake was very markedly reduced in the frontal cortex and hippocampus of the DSP-4 treated animals, whereas the decrease in the hypothalamus was smaller but still statistically significant. Dopamine uptake in the corpus striatum, as well as serotonin uptake in the frontal cortex, hippocampus and hypothalamus, were not influenced by DSP-4 treatment. Concomitantly, CCK receptor binding in certain brain regions was markedly affected. Thus, CCK receptor density was significantly higher in the frontal cortex and hippocampus of DSP-4-treated rats. If desipramine (25 mg/kg) was administered before DSP-4 treatment, the DSP-4-induced changes both in noradrenaline uptake and CCK receptor binding were not present, suggesting that both effects were exerted after uptake of the neurotoxin by the nerve terminals. The time-course of the development of changes in CCK-8 binding paralleled with some lag the development of changes in noradrenaline uptake. These findings demonstrate the denervation of noradrenergic input from the locus coeruleus induces certain alterations in the CCK-ergic neurotransmission. These alterations are similar to those seen in rats with deficits in response to novel stimuli, and may therefore mediate the neophobic responses observed in animals after lesions of noradrenergic innervation of the forebrain. Springer-Verlag, 1992 CCK receptors nationallicence DSP-4 nationallicence Locus coeruleus nationallicence Noradrenaline nationallicence Novelty-oriented behaviour nationallicence Harro Jaanus Department of Medical Pharmacology, Uppsala University, Biomedical Center, S-75124, Uppsala, Sweden aut Jossan Sukhwinder Department of Medical Pharmacology, Uppsala University, Biomedical Center, S-75124, Uppsala, Sweden aut Oreland Lars Department of Medical Pharmacology, Uppsala University, Biomedical Center, S-75124, Uppsala, Sweden aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/4(1992-10-01), 425-431 0028-1298 346:4<425 1992 346 210 https://doi.org/10.1007/BF00171085 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00171085 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Harro Jaanus Department of Medical Pharmacology, Uppsala University, Biomedical Center, S-75124, Uppsala, Sweden aut NATIONALLICENCE 700 1- Jossan Sukhwinder Department of Medical Pharmacology, Uppsala University, Biomedical Center, S-75124, Uppsala, Sweden aut NATIONALLICENCE 700 1- Oreland Lars Department of Medical Pharmacology, Uppsala University, Biomedical Center, S-75124, Uppsala, Sweden aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/4(1992-10-01), 425-431 0028-1298 346:4<425 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer