Memory deficits following internal capsule lesions in rats and their improvement by L-6-ketopiperidine-2-carbonyl-L-leucyl-L-proline amide (RGH-2202), a thyrotropin-releasing hormone analogue.
A memory deficit model has been developed following bilateral internal capsule lesions in rats. During 12-49 days after internal capsule lesions, the rats showed a marked impairment of active avoidance acquisition in a step-through apparatus, while they exhibited no observable change in native behaviors, except a slight increase in exploratory activity. A passive avoidance task in the same apparatus was also impaired in internal capsule lesioned rats when examined after one-trial training, though the task was gradually acquired by repeated trainings. Moreover, the retention of both the active and passive avoidance responses in well-trained rats deteriorated after internal capsule lesions. On the other hand, internal capsule-lesioned rats did not perform any worse than sham-operated rats in a T-maze spontaneous alternation behavior and in a habituation response to a novel environment. In the frontal cortex and striatum of internal capsule-lesioned rats, there was a significant decrease of dopamine, serotonin and their metabolites, but no change of acetylcholine levels. The acquisition deficit of active avoidance in internal capsule-lesioned rats was improved by thyrotropin-releasing hormone (TRH, 10 mg/kg, i.p.) and L-6-ketopiperidine-2-carbonyl-L-leucyl-L-proline amide (RGH-2202, 10 mg/kg, i.p., 0.2 and 1 mg/kg i.v.), but not by physostigmine sulfate (0.2 mg/kg, i.p.). These results indicate that bilateral internal capsule lesions in rats induce long-term memory deficits which are paralleled with a decrease of the contents of monoamines and their metabolites and improved by TRH and RGH-2202.
Oka
M
M
Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd., Suita/Osaka, Japan.
Ito
T
T
Furukawa
K
K
Karasawa
T
T
Kadokawa
T
T
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D004597:Electroshock; D005106:Exploratory Behavior / Q000187:drug effects; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000503:physiopathology*; D008960:Models, Psychological; D018377:Neurotransmitter Agents / Q000378:metabolism; D010830:Physostigmine; D011712:Pyramidal Tracts / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013238:Stereotaxic Techniques; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use
D018377:Neurotransmitter Agents; D013973:Thyrotropin-Releasing Hormone; C055448:posatirelin; D010830:Physostigmine