|
|
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char = .;code = 46
result sql = Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats.
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result sql = Performance on working memory tasks, a measure of prefrontal cortical function, is impaired by exposure to mild stress as well as the anxiogenic drug, FG7142. Previous studies have shown that like stress, FG7142 increases catecholamine release in the prefrontal cortex (PFC) and that high levels of dopamine (DA) D(1) and norepinephrine (NE) alpha-1 receptor stimulation underlie the FG7142-induced cognitive impairment. Both the FG7142-induced DA turnover and working memory deficit can be blocked by pretreatment with the nonselective NE alpha-2/imidazoline I1 receptor agonist, clonidine. The present study examined the alpha-2 adrenoceptor subtype underlying this reversal in FG7142-induced working memory deficits by comparing the efficacy of clonidine with the more selective alpha-2A adrenoceptor agonist, guanfacine. The anxiogenic drug, FG7142 (0, 10, 20, or 30 mg/kg), dose-dependently impaired delayed alternation performance. Clonidine pretreatment (0.1 mg/kg, 30 min prior to FG7142) partially reversed the FG7142-induced impairment while guanfacine pretreatment (0.11 mg/kg) completely blocked the FG7142-induced impairment. Neither clonidine nor guanfacine had any effect on performance when administered alone. This study suggests that stimulation of the NE alpha-2A receptor subtype is sufficient to ameliorate the cognitive deficit induced by FG7142. Clonidine's sedative and hypotensive side effects limit its therapeutic usefulness; however, selective alpha-2A receptor agonists may be effective in treating prefrontal cognitive deficits in stress-related neuropsychiatric disorders with fewer side effects.
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char = s;code = 115
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = o;code = 111
char = r;code = 114
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = x;code = 120
char = i;code = 105
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = ,;code = 44
char = ;code = 32
char = F;code = 70
char = G;code = 71
char = 7;code = 55
char = 1;code = 49
char = 4;code = 52
char = 2;code = 50
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = s;code = 115
char = .;code = 46
result sql = Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats.
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char = ;code = 32
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char = s;code = 115
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char = ;code = 32
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char = e;code = 101
char = s;code = 115
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char = D;code = 68
char = A;code = 65
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char = ;code = 32
char = D;code = 68
char = (;code = 40
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char = n;code = 110
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char = (;code = 40
char = N;code = 78
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char = ;code = 32
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char = s;code = 115
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char = e;code = 101
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char = ;code = 32
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char = m;code = 109
char = e;code = 101
char = l;code = 108
char = i;code = 105
char = o;code = 111
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = g;code = 103
char = n;code = 110
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char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = e;code = 101
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char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = ;code = 32
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char = ;code = 32
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char = l;code = 108
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char = i;code = 105
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = s;code = 115
char = ;code = 32
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char = e;code = 101
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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char = y;code = 121
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
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char = s;code = 115
char = ;code = 32
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char = i;code = 105
char = m;code = 109
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char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
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char = u;code = 117
char = t;code = 116
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char = ;code = 32
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char = s;code = 115
char = e;code = 101
char = f;code = 102
char = u;code = 117
char = l;code = 108
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char = l;code = 108
char = e;code = 101
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char = v;code = 118
char = e;code = 101
char = ;code = 32
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char = l;code = 108
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char = s;code = 115
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char = e;code = 101
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char = f;code = 102
char = e;code = 101
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char = v;code = 118
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char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
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char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
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char = e;code = 101
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = p;code = 112
char = s;code = 115
char = y;code = 121
char = c;code = 99
char = h;code = 104
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = r;code = 114
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = f;code = 102
char = e;code = 101
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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char = .;code = 46
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char = >;code = 62
result sql = Performance on working memory tasks, a measure of prefrontal cortical function, is impaired by exposure to mild stress as well as the anxiogenic drug, FG7142. Previous studies have shown that like stress, FG7142 increases catecholamine release in the prefrontal cortex (PFC) and that high levels of dopamine (DA) D(1) and norepinephrine (NE) alpha-1 receptor stimulation underlie the FG7142-induced cognitive impairment. Both the FG7142-induced DA turnover and working memory deficit can be blocked by pretreatment with the nonselective NE alpha-2/imidazoline I1 receptor agonist, clonidine. The present study examined the alpha-2 adrenoceptor subtype underlying this reversal in FG7142-induced working memory deficits by comparing the efficacy of clonidine with the more selective alpha-2A adrenoceptor agonist, guanfacine. The anxiogenic drug, FG7142 (0, 10, 20, or 30 mg/kg), dose-dependently impaired delayed alternation performance. Clonidine pretreatment (0.1 mg/kg, 30 min prior to FG7142) partially reversed the FG7142-induced impairment while guanfacine pretreatment (0.11 mg/kg) completely blocked the FG7142-induced impairment. Neither clonidine nor guanfacine had any effect on performance when administered alone. This study suggests that stimulation of the NE alpha-2A receptor subtype is sufficient to ameliorate the cognitive deficit induced by FG7142. Clonidine's sedative and hypotensive side effects limit its therapeutic usefulness; however, selective alpha-2A receptor agonists may be effective in treating prefrontal cognitive deficits in stress-related neuropsychiatric disorders with fewer side effects.
Publication: Pharmacol. Biochem. Behav. 2000 Nov ;67(3)::397-403.
Publication Date: 2000 Nov
Study Author(s): Birnbaum, S G;Podell, D M;Arnsten, A F;
Institution: Section of Neurobiology, Yale University School of Medicine, P.O. Box 208001, New Haven, CT 06520-8001, USA. [email protected]
Shortcut link to this study:
Publication Date: 2000 Nov
Study Author(s): Birnbaum, S G;Podell, D M;Arnsten, A F;
Institution: Section of Neurobiology, Yale University School of Medicine, P.O. Box 208001, New Haven, CT 06520-8001, USA. [email protected]
Shortcut link to this study:
Performance on working memory tasks, a measure of prefrontal cortical function, is impaired by exposure to mild stress as well as the anxiogenic drug, FG7142. Previous studies have shown that like stress, FG7142 increases catecholamine release in the prefrontal cortex (PFC) and that high levels of dopamine (DA) D(1) and norepinephrine (NE) alpha-1 receptor stimulation underlie the FG7142-induced cognitive impairment. Both the FG7142-induced DA turnover and working memory deficit can be blocked by pretreatment with the nonselective NE alpha-2/imidazoline I1 receptor agonist, clonidine. The present study examined the alpha-2 adrenoceptor subtype underlying this reversal in FG7142-induced working memory deficits by comparing the efficacy of clonidine with the more selective alpha-2A adrenoceptor agonist, guanfacine. The anxiogenic drug, FG7142 (0, 10, 20, or 30 mg/kg), dose-dependently impaired delayed alternation performance. Clonidine pretreatment (0.1 mg/kg, 30 min prior to FG7142) partially reversed the FG7142-induced impairment while guanfacine pretreatment (0.11 mg/kg) completely blocked the FG7142-induced impairment. Neither clonidine nor guanfacine had any effect on performance when administered alone. This study suggests that stimulation of the NE alpha-2A receptor subtype is sufficient to ameliorate the cognitive deficit induced by FG7142. Clonidine's sedative and hypotensive side effects limit its therapeutic usefulness; however, selective alpha-2A receptor agonists may be effective in treating prefrontal cognitive deficits in stress-related neuropsychiatric disorders with fewer side effects.
PMID: 11164065
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