domoic-acid and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic-acid

We have previously reported that neonatal rats display enhanced sensitivity to domoic acid relative to adults, and that perinatal injections of low doses of domoic acid alter early associational learning in the newborn rat. The current study was designed to further investigate the effects of low dose domoic acid on neonatal odour conditioning and to determine if the observed effects are due in part to an action on NMDA receptors. Groups of rat pups were conditioned to a novel odour on postnatal day (PND) 8, injected with 20 microg/kg domoic acid either alone, or in combination with the NMDA antagonist CPP (or appropriate controls), daily from day 8-14, re-exposed to the conditioning odour or a novel odour on day 9, and tested for odour preference on day 13 using a standard 3-choice paradigm. Results indicated that rats treated with domoic acid spent significantly more time over the conditioning odour than did saline-treated rats when tested on PND 13. This effect was antagonized by concomitant injection of CPP, indicating an involvement of NMDA receptors in the actions of DOM in this paradigm. Rats injected with either saline or CPP alone showed the opposite effect, i.e. a preference for the alternate odour. The results indicate that a very low dose of DOM produces a conditioned odour preference in neonatal rats and that this effect is due in part to NMDA receptor involvement, thereby emphasizing a role for both kainate and NMDA glutamate receptors in implicit memory.

Topics: Animals; Animals, Newborn; Excitatory Amino Acid Antagonists; Female; Kainic Acid; Male; Memory; Neuromuscular Depolarizing Agents; Odorants; Piperazines; Rats; Rats, Sprague-Dawley; Receptors, Kainic Acid; Receptors, N-Methyl-D-Aspartate; Smell

1. Neuropharmacological actions of several kainate derivatives (kainoids) were examined for electrophysiological effects in the isolated spinal cord and the dorsal root fibre of the newborn rat. 2. Some kainoids caused depolarization of the motoneurone much more effectively than kainic acid or domoic acid and others were weaker. The rank order of the depolarizing activities of the kainoids tested here is as follows: 4-(2-methoxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (MFPA) greater than acromelic acid A greater than domoic acid greater than or equal to 4-(2-hydroxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (HFPA) greater than or equal to acromelic acid B greater than kainic acid. 3. In the isolated dorsal root fibre, domoic acid caused the most significant depolarization. There were distinct differences with regard to the rank order of the depolarizing activity between the motoneurone and the dorsal root fibre. The rank order in the dorsal root fibre is domoic acid greater than acromelic acid B greater than 5-bromowillardiine greater than or equal to MFPA greater than acromelic acid A greater than HFPA greater than kainic acid. 4. Significant desensitization of kainate receptors was observed in the isolated dorsal root fibre during prolonged application of L-glutamate, kainate and its derivatives. Cross desensitization was also observed among these excitatory amino acids. Receptors desensitized by kainate did not respond to MFPA, HFPA and acromelic acids, suggesting that these kainate derivatives activated common kainate receptors in the dorsal root fibre.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Animals, Newborn; In Vitro Techniques; Kainic Acid; Motor Neurons; Neuromuscular Depolarizing Agents; Piperazines; Quinoxalines; Rats; Rats, Inbred Strains; Receptors, N-Methyl-D-Aspartate; Spinal Cord; Structure-Activity Relationship