['leading', 'to', 'secretion', 'of', 'ACTH', 'which', 'rapidly', 'desensitizes.', 'In', 'vivo', 'microdialysis', 'studies', 'show', 'that', 'nicotine', 'stimulates', 'norepinephrine', 'secretion', 'in', 'the', 'hypothalamic', 'paraventricular', 'nucleus', '(PVN);', 'this', 'undergoes', 'rapid,', 'though', 'partial', 'desensitization.', 'Nicotine', 'stimulates', 'ACTH', 'when', 'selectively', 'infused', 'into', 'catecholaminergic', 'brainstem', 'regions,', 'and', 'i.v.', 'nicotine', 'induces', 'cfos', 'protein', 'expression,', 'an', 'indicator', 'of', 'acute', 'neuronal', 'activation,', 'in', 'the', 'same', 'brainstem', 'areas.', 'The', 'role', 'of', 'PVN', 'neuropeptides,', 'such', 'as', 'CRF,', 'oxytecin', 'and', 'vasopressin,', 'in', 'nicotine-stimulated', 'ACTH', 'secretion', 'will', 'be', 'defined', 'using', 'cfos/neuropeptide', 'colocalization', 'to', 'identify', 'activated', 'parvocellular', 'PVN', 'neurons.', 'Additional', 'approaches', 'to', 'identify', 'the', 'neuropeptides', 'involved', 'include', '(1)', 'the', 'peripheral', 'delivery', 'of', 'specific', 'peptide', 'receptor', 'antagonists', 'and', 'antisera', 'to', 'inhibit', 'ACTH', 'xesponses', 'to', 'nicotine,', 'and', '(11)', 'measurement', 'of', 'CRF', 'depletion', 'from', 'the', 'median', 'eminence', 'in', 'colchicine', 'pretreated', 'animals', 'as', 'an', 'index', 'of', 'CRF', 'secretion.', 'Whether', 'nicotine-induced', 'norepinephrine', 'release', 'uniformly', 'Finally,', 'desensitization', 'of', 'the', 'ACTH', 'response', 'to', 'norepinephrine', 'or', 'epinephrine,', 'administered', 'into', 'the', 'third', 'ventricle,', 'will', 'be', 'evaluated', 'to', 'determine', 'whether', 'this', 'contributes', 'to', 'the', 'desenaitization', 'of', 'the', 'ACTH', 'xesponse', 'to', 'nicotine.', 'The', 'second', 'aim', 'of', 'the', 'proposal', 'is', 'to', 'compare', 'the', 'brainstem-PVN-neurocendocrine', 'effects', 'of', 'nicotine', 'to', 'another', 'nicotine-reaponsive', 'xegion,', 'the', 'hippocampal', 'complex,', 'which', 'is', 'potentially', 'involved', 'in', 'the', 'effects', 'of', 'nicotine', 'on', 'memory.', 'Nicotine', 'also', 'stimulates', 'norepinephrine', 'secretion', 'and', 'cfosa', 'expression', 'in', 'the', 'hippocampus,', 'although', 'the', 'dose-response', 'characteristics', 'are', 'diatinctively', 'different', 'and', 'desensitization', 'of', 'the', 'norepinephrine', 'response', 'is', 'not', 'observed,', 'in', 'compariaon', 'to', 'the', 'PVN.', 'These', 'differences', 'can', 'be', 'explored', 'in', 'pharmacological', 'studies', 'using', 'nicotinic', 'cholinergic', 'agonists', 'and', 'antagonists', 'which', 'distinguish', 'different', 'aubtypes', 'of', 'neuronal', 'nicotinic', 'receptors', 'to', 'determine', 'whether', 'different', 'receptors', 'mediate', 'PVN', 'vs', 'hippocampal', 'norepinephrine', 'secretion,', 'Whether', 'brainstem', 'catecholaminergic', 'systems', 'mediate', 'these', 'PVN', 'va', 'hippocampal', 'responses', 'will', 'be', 'evaluated', 'by', 'injecting', 'nicotine', 'into', 'brainstem', 'regions', 'and', 'measuring', 'norepinephrine', 'secretion', 'and', 'the', 'expression', 'of', 'cfos', 'protein.', 'cFos', 'expression', 'will', 'also', 'be', 'used', 'to', 'determine', 'whether', '“cross-talk”', 'occurs', 'between', 'brainstem', 'catecholaminergic', 'regions', 'in', 'response', 'to', 'local', 'nicotine.', 'Thus,', 'comparison', 'of', 'the', 'PVN', 'and', 'the', 'hippocampus', 'will', 'provide', 'new', 'insights', 'into', 'mechanisms', 'underlying', 'the', 'differential', 'effects', 'of', 'nicotine', 'on', 'brain', 'function.', '6/7/469', 'DIALOG(R)File', '266:Fed.', 'Res.', 'in', 'Progress', '{c)', 'format', 'only', '1995', 'Dialeg', 'Info.Sves.', 'All', 'rts.', 'reserv.', '0123965', 'IDENTIFYING', 'NO.:', 'SRO1DA03976-10', 'AGENCY', 'CODE:', 'CRISP', 'DRUG', 'ABUSE', 'PREVENTION--ADOLESCENCE', 'AND', 'EARLY', 'ADULTHOOD', 'PRINCIPAL', 'INVESTIGATOR:', 'PENTZ,', 'MARY', 'A', 'ADDRESS:', 'UNIV', 'OF', 'SOUTHERN', 'CALIFORNIA', '1000', 'S$', 'FREMONT', 'AVE,', 'SUITE', '641', 'ALHAMBRA,', 'CA', '91803-1358', 'PERFORMING', 'ORG.:', 'UNIVERSITY', 'OF', 'SOUTHERN', 'CALIFORNIA,', 'LOS', 'ANGELES,', 'CALIFORNIA', 'SPONSORING', 'ORG.:', 'NATIONAL', 'INSTITUTE', 'ON', 'DRUG', 'ABUSE', 'Fy', ':', '94', 'FUNDS:', '$1,307,669', 'TYPE', 'OF', 'AWARD:', 'Noncompeting', 'Continuation', '(Type', '5)', ':', 'SUMMARY:', 'The', 'proposed', 'project', 'is', 'a', 'long-term', 'evaluation', 'of', 'an', 'ongoing', 'community-', 'based', 'drug', 'abuse', 'prevention', 'program', 'Midwestern', 'Prevention', 'Project)', 'that', 'has', 'emphasized', 'intervention', 'with', 'young', 'during', 'early', 'adolescence,and', 'experimental', 'test', 'of', 'additional', 'program', 'components', 'as', 'these', 'youth', 'move', 'into', 'late', 'adolescence.', 'Analyzed', 'through', 'three', 'year', 'follow-up,', 'the', 'program', 'has', 'produced', 'significant', 'reductions', 'in', 'monthly', 'and', 'weekly', 'use', 'ef', 'tobacco,', 'alcohol,', 'marijuana;', 'by', 'three', 'year', 'follow-up,', 'effects', 'on', 'monthly', 'cocaine', 'use', 'and', 'lifetime', 'amphetamine', 'use', 'are', 'also', 'significant.', 'Effects', 'are', 'UaT', ' ', '51140', '2817']