Pavlovian conditioning of the rabbit's nictitating membrane response, a corneal-VIth nerve reflex, is generally agreed to provide a reliable measure of associative learning and memory. This model system will be used to identify the anatomical pathways and neurochemical systems involved in learning and memory and to examine the behavioral and neurochemical processes through which drugs act to alter learning and memory. Experiments will be carried out under three major aims that will provide converging approaches to origin additional knowledge of these basic processes.
Aim 1 will examine those brain regions that have been suggested to play an essential or important role in the acquisition and/or performance of conditioned responses. This will include a thorough examination of recent proposals that the cerebellum is essential for the learning of motor acts by the use of cortical (VIth lobe) and subcortical (interpositus) lesions of the cerebellum and from reversible lesions produced by infusion of lidocaine. The reversible lesion will then be employed to establish whether interpositus is essential for the acquisition of conditioned responses. These reversible lesions will also be used to identify other pathways of the conditioned and unconditioned response.
Aim 2 will examine the uptake of 3H- and 14C-2-deoxy-D-glucose in a double isotope technique employing quantitative autoradiography to identify the areas of brain that are differentially activated by the contiguous presentation of a conditioned and unconditioned stimulus and whether such heterosynaptic facilitation of neuronal activity can predict subsequent rates of learning. For example, the effect of some drugs on learning appear to be secondary to their ability to increase or decrease such heterosynaptic facilitation.
Aim 3 will use intraventricular injections of drugs that activate or inhibit the cAMP system to examine the role of this second messenger in learning and in the effects of drugs on learning. Such knowledge should provide clues concerning the neural systems involved in human disorders of learning and memory (e.g., Alzheimer's disease) and identify the drugs that might be effective in their treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH016841-25
Application #
3486343
Study Section
Special Emphasis Panel (SRCM (14))
Project Start
1988-09-01
Project End
1993-08-31
Budget Start
1992-09-30
Budget End
1993-08-31
Support Year
25
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Allegheny University of Health Sciences
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19129
Schindler, Emmanuelle A D; Harvey, John A; Aloyo, Vincent J (2013) Phospholipase C mediates (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-, but not lysergic acid diethylamide (LSD)-elicited head bobs in rabbit medial prefrontal cortex. Brain Res 1491:98-108
Schindler, Emmanuelle A D; Dave, Kuldip D; Smolock, Elaine M et al. (2012) Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Pharmacol Biochem Behav 101:69-76
Scarlota, Laura C; Harvey, John A; Aloyo, Vincent J (2011) The role of serotonin-2 (5-HT2) and dopamine receptors in the behavioral actions of the 5-HT2A/2C agonist, DOI, and putative 5-HT2C inverse agonist, SR46349B. Psychopharmacology (Berl) 213:393-401
Romano, Anthony G; Quinn, Jennifer L; Li, Luchuan et al. (2010) Intrahippocampal LSD accelerates learning and desensitizes the 5-HT(2A) receptor in the rabbit, Romano et al. Psychopharmacology (Berl) 212:441-8
Oristaglio, Jeff; Romano, Anthony G; Harvey, John A (2009) Amphetamine influences conditioned response timing and laterality of anterior cingulate cortex activity during rabbit delay eyeblink conditioning. Neurobiol Learn Mem 92:1-18
Aloyo, V J; Berg, K A; Spampinato, U et al. (2009) Current status of inverse agonism at serotonin2A (5-HT2A) and 5-HT2C receptors. Pharmacol Ther 121:160-73
Romano, A G; Du, W; Harvey, J A (1994) Methylenedioxyamphetamine: a selective effect on cortical content and turnover of 5-HT. Pharmacol Biochem Behav 49:599-607
Chen, J F; Aloyo, V J; Qin, Z H et al. (1994) Irreversible blockade of D2 dopamine receptors by fluphenazine-N-mustard increases D2 dopamine receptor mRNA and proenkephalin mRNA and decreases D1 dopamine receptor mRNA and mu and delta opioid receptors in rat striatum. Neurochem Int 25:355-66
Chen, J F; Aloyo, V J; Weiss, B (1993) Continuous treatment with the D2 dopamine receptor agonist quinpirole decreases D2 dopamine receptors, D2 dopamine receptor messenger RNA and proenkephalin messenger RNA, and increases mu opioid receptors in mouse striatum. Neuroscience 54:669-80
Harvey, J A; Welsh, J P; Yeo, C H et al. (1993) Recoverable and nonrecoverable deficits in conditioned responses after cerebellar cortical lesions. J Neurosci 13:1624-35

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