The non-competitive N-methyl-d-aspartate (NMDA) antagonist MK-801, injected intraperitoneally at 0.1 mg/kg, at times between 1 h before and 5 min after training chicks on a one-trial passive avoidance task, resulted in amnesia for the task on test 3 or 24 h subsequently. No amnesia was apparent at 24 h if chicks were injected between 1 and 6 h after training. Amnesia did not develop immediately; it was not apparent 30 min after training in chicks injected 5 min after training. At this dose of MK-801 no other effects on motor or pecking behaviour of the birds were observed. Bilateral or unilateral intracerebral injections of 1.5 nM MK-801 5 min after training produced a similar amnesia at 3 h to that of intraperitoneally injected MK-801; no hemispheric differences were observed, presumably because of the ready diffusion of the MK-801. By contrast, intracerebral injections of the non-NMDA glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 6,7-nitro-7-sulphamoyl-benzoquinoxaline-2,3-dione (NBQX) (0.066 microM) 5 min after training, despite producing severe if transient behavioural disturbances, were without effect on retention for the avoidance response in chicks tested 3 h subsequently. We interpret these results as pointing to a requirement for NMDA, but not kainate or quisqualate, receptor activation as an early enabling event in the biochemical cascade required for long-term memory formation for passive avoidance in the chick.
The effects of new cyclic analogs of ACTH fragments, EHFRWGKPVG-NH2 and KHFRWG-NH2, which have specific and nonspecific active centers in their structure, in the self-stimulation, avoidance, and grooming behavior of rabbits were investigated in this study. The intraventricular administration of EHFRWGKPVG-NH2 in doses of 0.1-2.5 micrograms increased the frequency of self-stimulation (SS), while in doses of 4-5 micrograms, it decreased the frequency of self-stimulation. The administration of KHFRWG-NH2 in doses of 0.1-5.o micrograms, induced a decrease in the frequency of SS by 25-30% in the first 15 min following the injections; this indicator returned to the baseline level thereafter, and decreased again. SS was more intense after 24-48 h, 5-8% higher than the baseline level, and remained practically unchanged over the course of a two-hour experiment. The administration of the EHFRWGKPVG-NH2 fragment in doses of 0.5-2.0 micrograms increased the latent period of the avoidance reaction, decreased the time of the anxiety state, and increased the time of the comfort state. In addition to these changes, both ACTH fragments induced intense grooming, increased the duration of grooming by 200-400% as compared with the control animals which were administered physiological solution.
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