The classical (Pavlovian) conditioning of the rabbit nictitating membrane response (NMR) provides and unambigious measure of the full range of associative learning and memory and, therefore, is ideal for examining the behavioral and neural mechanisms through which drugs act to alter associative processes as well as for examining the neurochemical processes underlying learning. We will use converging approaches to obtain additional knowledge of such basic processes.
Aim 1 will continue our investigations of the anatomical pathway(s) through which auditory stimuli exert their unconditioned and conditioned excitatory effects on the nictitating membrane reflex through the use of the retrograde transport of HRP and anterograde transport of tritiated amino acids, as well as electrolytic lesions, knife cuts, reversible blockade through infusion of a local anesthetic, electrical stimulation, and unit recording at relevant loci.
Aim 2 will further examine our findings suggesting that reflex facilitation forms the basis of learning and that drugs enhance or retard the rate of learning by increasing or decreasing reflex facilitation.
Aim 3 will continue studies employing tritiated 2-DG in order to determine whether the differences in metabolic (and hence presumably neuronal) activity of the dorsal cochlear nucleus, in animals receiving paired vs. unpaired presentations of tones and air puff, reflects a difference in the excitatory properties of the tone conditioned stimulus as a result of learning. In addition, we will determine whether drugs that enhance or retard the rate of learning will affect these differences in metabolic activity.
Aim 4 represents our attempt to detail the possible role of second messenger system (e.g., cAMP) in regulating the biophysical events that lead to learning and in mediating the effects of drugs on learning. The results of this research should provide insights into the manner by which various psychopharmacologic agents affect associative processes in humans.

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National Institute of Mental Health (NIMH)
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University of Iowa
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Iowa City
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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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