Neuropeptides and the blood-brain barrier in goldfish

The general activity level of a goldfish is easily monitored by placing it in water to a depth of 2.5 cm in an aquarium on top of an activity meter. With this system, goldfish were administered a 5 microliter (80 microgram/kg) intracranial (IC) or intraperitoneal (IP) injection of one of 21 compounds and tested for general activity. The results indicated that activity decreased significantly over time and the peptides differentially decreased activity, with the greatest alterations in activity produced by two new enkephalin analogs: D-Ala2, F5Phe4-enkephalin-NH2 and Nalpha Nepsilon-bis-(D-Ala2-enkephalin)-Lys-NH2. Overall, decreased activity began approximately 3 min after an IC injections and 6 min after an IP injection. The longer latency after IP injections may indicate the time required for the substance, either in its original or fragmented form, to reach and cross the blood-brain barrier and makes a primary peripheral effect unlikely. Most of the peptides or possibly their metabolites appeared to enter the brain since no significant difference in activity existed after IC and IP injections, with both producing reliable decreases from the control. In summary, peptides can exert behavioral effects after both IC and IP administration in goldfish.