Farm or laboratory for male chicks?
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Biomedical subjects
Publications and source records attributed to A Cherkin.
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Three experiments describe retroactive memory enhancement in chicks by chlorpromazine (CPZ), a potent membrane stabilizer at anesthetic doses. First, chicks trained on a one-trial peck suppression task under moderate aversant conditions and given 60--144 mg CPZ/kg, intraperitoneally, displayed increased memory retention 24 h later when compared with chicks given saline or 15--36 mg CPZ/kg. The second experiment confirmed the memory enhancement using a different moderate aversant on a different peck target and extended the effect to 48 h. The third experiment demonstrated the CPZ effect to be retrograde because the enhancement observed when CPZ was injected 1 min or 3 min after training did not occur when injection was delayed 4 h. One speculative interpretation of retrograde enhancement with CPZ includes the stabilization of swollen dendritic spines, which may facilitate neuronal pathways.
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L-proline induces retroactive amnesia without causing brain seizures or isoelectric activity. 3,4-dehydro-DL-proline, a proline analog containing a double-bond in the 5-membered ring, has similar effects at a smaller dose. Three experiments describe the amnestic qualities of 3,4-dehydro-DL-proline in a chick memory paradigm, the retrograde quality of this amnesia, and its existence in a mammalian (mouse) preparation. Finally, EEG records show that chicks injected with amnestic doses of 3,4-dehydro-DL-proline do not exhibit seizure spiking or abnormal electrical activity.
The effects of L-proline, D-proline, and L-azetidine-2-carboxylic acid (L-A.2.C., the lower homolog of L-proline) have been compared in two systems. L-Proline is more potent than either analog in causing amnesia of one-trial avoidance conditioning of the 2-day-old chick and in preventing mechanically induced spreading depression in the retina isolated from 2-3-week-old chicks. The results suggest that the L-configuration and the proper molecular size are essential for the effects of L-proline upon memory and upon spreading depression. This level of specificity is greater than that involved in protein synthesis because L-A.2.C. is incorporated into protein in place of L-proline, in several protein-synthesizing systems.
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Two- and five-day old chicks were injected intraventricularly with D-proline and structurally related compounds. D-proline produced convulsions and lethality, but was non-amnestic, whereas the naturally-occurring isomer, L-proline, was non-convulsant and non-toxic but amnestic. D-proline convulsions were accompanied by decreased high frequency in the EEG and increased slow wave activity. High amplitude spiking was not observed. The lethality of D-proline was saline-dependent. Control experiments ruled out possible toxic factors such as hypertonicity, pH pyrogens, injection volume, or needle misplacement. The results demonstrate that saline and distilled water are not equivalent injection vehicles. A sodium-free vehicle may lead to artifacts but is advantageous in experiments in which amino acid transport must be minimized.
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The lysosome hypothesis of aging predicts that membrane stabilizers will extend life-span. Stabilizers containing the dimethylaminoethanol moiety (DMAE) have been reported to extend the life-span of drosophila and mice. We tested the prediction in Japanese quail (N = 15) by administering DMAE bitartrate (18.4 mg/kg/day) in the drinking water for 69 weeks, starting at 195 weeks of age. A matched control group (N = 14) received tartaric acid (4.0 mg/kg/day) in the water. Contrary to the prediction, the DMAE-treated group has a shorter life-span after start of treatment (49 weeks) than the controls (69 weeks). No significant differences between the groups were observed in body weight or daily fluid intake. Three behavioral studies were carried out on survivors at 243-249 weeks of age, namely; activity response to light-flash; sexual mounting response to a female quail; and classical conditioning of the heart rate. Aged quail differed from young-adults in changes in motor activity in response to light flashes. Aged quail appeared less responsive initially to reinforced conditioning trials and demonstrated extinction when light flash was not followed by electric shock. There were no detectable differences in latency to mount or in basal heart rate, either as a function of age or as a function of DMAE treatment.
Intracerebral injection of L-proline, 1 minute after one-trial avoidance training of chicks, impaired memory 24 hours later. Chicks injected with proline 1 or 4 hours after training and controls injected with L-isoleucine at intervals after training, showed no impairment of memory 24 hours after training. The retrograde impairment of long-term memory induced by proline occurred without the convulsions or electrographic events usually associated with retrograde amnesic treatments.
Fingerling rainbow trout (N = 436) were trained in one trial with brief electric shock (2.0 V/cm) to suppress their spontaneous upstream swimming into a quiet well. Memory retention one day later was not influenced by the temperature at which they had been acclimated, trained and tested (10 degrees C, 15 degrees C or 20 degrees C). When exposed 4 min after training for 2 min, to a flurothyl solution (10, 25, 50, 100 or 200 mul/l) trout convulsed and overturned. The onset of overturn was concentration- and temperature-dependent. Flurothyl altered the one-day retention of avoidance behavior; low concentrations enhanced, whereas high concentrations impaired. Memory-enhancing low concentrations of flurothyl, applied after post-training amnesic treatment with carbon dioxide, reversed the carbon dioxide amnesia.
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Strong flurothyl treatment (1.7% v/v for 8 min) produces retrograde amnesia in chicks when administered as long as 24 hr after one-trial avoidance training with a strongly aversive stimulus. Mild flurothyl treatment (0.2% v/v for 8 min) produced retrograde enhancement when administered as long as 16 min after similar training with a moderately aversive stimulus. The moderate training followed by mild flurothyl treatment enhanced 24-hr retention to the level found after strong training alone. Enhanced retention persisted for at least 72 hr; nonspecific performance effects faded within 48 hr. The predominant dose-dependent and time-dependent enhancement effect of mild flurothyl treatment is interpreted as improved memory consolidation.
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