Phosphodiesterase 4 inhibitors for cognitive and motor rehabilitation
The present invention provides methods of improving cognitive and motor deficits associated with central nervous system (CNS) disorder or condition in an animal. The methods comprise a general administration of phosphodiesterase 4 inhibitors and optionally training the animal under conditions sufficient to produce an improvement in performance.
1. A method comprising:
(a) providing cognitive training to an animal having a central nervous system disorder or condition under conditions sufficient to produce an improvement in performance by said animal of a cognitive task whose deficit is associated with said central nervous system (CNS) disorder or condition, wherein said deficit is a memory deficit;
(b) administering in conjunction with said cognitive training a phosphodiesterase inhibitor that enhances CREB pathway function during said cognitive training;
(c) repeating said providing and administering of steps (a) and (b) one or more times; and
(d) reducing the number of training sessions sufficient to produce said improvement in performance relative to the improvement in performance produced by cognitive training alone;
wherein said CNS disorder or condition is a neurodegenerative disease or condition; and
wherein said phosphodiesterase inhibitor is HT-0712:
wherein “Me” means “methyl” and “cPent” means “cyclopentyl” or an enantiomer or a mixture thereof.
2. The method of claim 1 , wherein said animal is a human.
3. A method comprising:
(a) training an animal under conditions sufficient to stimulate neuronal activity or a pattern of neuronal activity underlying one or more neuronal circuits in an animal;
(b) administering in conjunction with said training a phosphodiesterase inhibitor that enhances CREB pathway function during said training;
(c) repeating said training and administering of steps (a) and (b) one or more times; and
(d) reducing the number of training sessions sufficient to provide an improvement in function in said one or more neuronal circuits in said animal relative to the improvement in function produced by training alone;
wherein said animal has a memory deficit associated with a neurodegenerative disease or condition; and
wherein said phosphodiesterase inhibitor is HT-0712:
wherein “Me” means “methyl” and “cPent” means “cyclopentyl” or an enantiomer or a mixture thereof.
4. The method of claim 3 , wherein said animal is a human.
5. The method of claim 1 , wherein said cognitive training comprises spaced training sessions.
6. The method of claim 3 , wherein said training comprises spaced training sessions.
7. The method of claim 5 , wherein said phosphodiesterase inhibitor is administered before one or more training sessions.
8. The method of claim 6 , wherein said phosphodiesterase inhibitor is administered before one or more training sessions.