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char = G;code = 71
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char = B;code = 66
char = A;code = 65
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result sql = Abused inhalants enhance GABA-mediated synaptic inhibition.
Abused inhalants enhance GABA-mediated synaptic inhibition.
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char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = i;code = 105
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = o;code = 111
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = A;code = 65
char = B;code = 66
char = A;code = 65
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = G;code = 71
char = A;code = 65
char = B;code = 66
char = A;code = 65
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = a;code = 97
char = l;code = 108
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = a;code = 97
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = p;code = 112
char = u;code = 117
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = C;code = 67
char = A;code = 65
char = 1;code = 49
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = N;code = 78
char = Q;code = 81
char = X;code = 88
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = A;code = 65
char = P;code = 80
char = V;code = 86
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = a;code = 97
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = G;code = 71
char = P;code = 80
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = ;code = 32
char = G;code = 71
char = A;code = 65
char = B;code = 66
char = A;code = 65
char = (;code = 40
char = B;code = 66
char = );code = 41
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = o;code = 111
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = a;code = 97
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = G;code = 71
char = A;code = 65
char = B;code = 66
char = A;code = 65
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = a;code = 97
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = P;code = 80
char = S;code = 83
char = C;code = 67
char = );code = 41
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = a;code = 97
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = d;code = 100
char = m;code = 109
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = c;code = 99
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = u;code = 117
char = x;code = 120
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = -;code = 45
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 = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = I;code = 73
char = P;code = 80
char = S;code = 83
char = C;code = 67
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = e;code = 101
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = k;code = 107
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = y;code = 121
char = a;code = 97
char = n;code = 110
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = b;code = 98
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result sql = Abused inhalants are widely used, especially among school-age children and teenagers, and are 'gateway' drugs leading to the abuse of alcohol and other addictive substances. In spite of this widespread use, little is known about the effects produced by inhalants on the central nervous system. The similarity in behavioral effects produced by inhalants and inhaled anesthetics, together with their common chemical features, prompted this study of inhalant actions on a well-characterized anesthetic target, GABA synapses. Whole-cell patch clamp recordings were conducted on CA1 pyramidal neurons in rat hippocampal brain slices to measure effects on resting membrane properties, action potential discharge, and GABA-mediated inhibitory responses. Toluene, 1,1,1-trichloroethane, and trichloroethylene depressed CA1 excitability in a concentration-dependent and reversible manner. This depression appeared to involve enhanced GABA-mediated inhibition, evident in its reversal by a GABA receptor antagonist. Consistent with this, the abused inhalants increased inhibitory postsynaptic potentials produced using minimal stimulation of stratum radiatum inputs to CA1 neurons, in the presence of CNQX and APV to block excitatory synaptic responses and GGP to block GABA(B) responses. The enhanced inhibition appeared to come about by a presynaptic action on GABA nerve terminals, because spontaneous inhibitory postsynaptic current (IPSC) frequency was increased with no change in the amplitude of postsynaptic currents, both in the presence and absence of tetrodotoxin used to block interneuron action potentials and cadmium used to block calcium influx into nerve terminals. The toluene-induced increase in mIPSC frequency was blocked by dantrolene or ryanodine, indicating that the abused inhalant acted to increase the release of calcium from intracellular nerve terminal stores. This presynaptic action produced by abused inhalants is shared by inhaled anesthetics and would contribute to the altered behavioral effects produced by both classes of drugs, and could be especially important in the context of a disruption of learning and memory by abused inhalants.

Publication: Neuropsychopharmacology 2009 Sep ;34(10)::2296-304. :doi: 10.1038/npp.2009.57.
Publication Date: 2009 Sep
Study Author(s): MacIver, M Bruce;
Institution: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305-5117, USA. [email protected]
Shortcut link to this study:
Abused inhalants are widely used, especially among school-age children and teenagers, and are 'gateway' drugs leading to the abuse of alcohol and other addictive substances. In spite of this widespread use, little is known about the effects produced by inhalants on the central nervous system. The similarity in behavioral effects produced by inhalants and inhaled anesthetics, together with their common chemical features, prompted this study of inhalant actions on a well-characterized anesthetic target, GABA synapses. Whole-cell patch clamp recordings were conducted on CA1 pyramidal neurons in rat hippocampal brain slices to measure effects on resting membrane properties, action potential discharge, and GABA-mediated inhibitory responses. Toluene, 1,1,1-trichloroethane, and trichloroethylene depressed CA1 excitability in a concentration-dependent and reversible manner. This depression appeared to involve enhanced GABA-mediated inhibition, evident in its reversal by a GABA receptor antagonist. Consistent with this, the abused inhalants increased inhibitory postsynaptic potentials produced using minimal stimulation of stratum radiatum inputs to CA1 neurons, in the presence of CNQX and APV to block excitatory synaptic responses and GGP to block GABA(B) responses. The enhanced inhibition appeared to come about by a presynaptic action on GABA nerve terminals, because spontaneous inhibitory postsynaptic current (IPSC) frequency was increased with no change in the amplitude of postsynaptic currents, both in the presence and absence of tetrodotoxin used to block interneuron action potentials and cadmium used to block calcium influx into nerve terminals. The toluene-induced increase in mIPSC frequency was blocked by dantrolene or ryanodine, indicating that the abused inhalant acted to increase the release of calcium from intracellular nerve terminal stores. This presynaptic action produced by abused inhalants is shared by inhaled anesthetics and would contribute to the altered behavioral effects produced by both classes of drugs, and could be especially important in the context of a disruption of learning and memory by abused inhalants.
PMID: 19494804

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