Cortical amino acid neurotransmitter release is altered by CCK perfused in frontal region of unrestrained aged rats.
The purpose of this study was to investigate in the aged animal the functional interaction between cholecystokinin (CCK) and amino acid neurotransmitter activity in the frontal cortex, a structure of importance in age-related disabilities. Guide cannula for repeated push-pull perfusion were implanted bilaterally in the superficial frontal cortex of male Sprague-Dawley rats. Two groups of animals were selected on the basis of their age at the time of stereotaxic surgery: 90 days and two years. Following post-operative recovery, an artificial CSF solution was perfused repeatedly within the cortex of each animal for a 5.0 min interval. The rate of perfusion was 25 microliters/min and a 5.0 min period elapsed between the collection of each sample of perfusate. After the initial control perfusions, CCK octapeptide was incorporated in a concentration of 6.0 or 18.0 ng/microliter in the CSF and perfused for 5.0 min under identical conditions. Each sample of perfusate was assayed by high performance liquid chromatography with electrochemical detection (HPLC-EC) for its content of glutamate (Glu), aspartate (Asp), glutamine (Gln), glycine (Gly), taurine (Tau) and gamma-amino-butyric acid (GABA) with homoserine used as an internal standard. Although CCK in the lower 6.0 ng/microliter concentration failed to alter significantly the profile of amino acids in the frontal cortex, the higher 18.0 ng/microliter solution of CCK enhanced the efflux of Glu as well as Asp, but only in the aged rats. Both concentrations of CCK tended also to augment the release of Gln in the older animals but these changes were not statistically significant. Both Gly and Tau were unaffected by CCK in either dose in both the young and old groups. GABA was not detectable in any of the samples of perfusate throughout the experiments. These results suggest that CCK-8 exerts a selective effect on amino acid neurotransmitter activity in the frontal cortex which is clearly age-dependent. In the older animal, this sensitivity of the cortical cells to CCK may reflect a functional attribute of the peptide in the aging process.
D000375:Aging; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D018377:Neurotransmitter Agents; D002766:Cholecystokinin