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Receptors modulation by chronic imipramine treatment
2055 O.th.31.3 ]
Receptors modulation by chronic imipram~ne treatment De Montis, G.M., Devoto, P., Meloni, D., Saba~ P. and Tag!iamonte, A. Institute of Pharmacology and Biochemical Pathology, University of Cagliari, via Porceli 4. 09124 Cagliari. Italy Long term administration of imipramine to rats produced an increase of adenylate cyclase Vmax restricted to the imbic areas. This effect was prevented by the daily administration of a-methyl-p-tyrosine (a-MPT). associated to mipramine and given at a dose (50 mg/kg) which per s~ had no effect on adenylate cyclase activity. A time course of chronic imipramine effects on dopaminergic transmission in the limbic area showed that the tecrease of both D-i receptor number and adenylate cyclase stimulation by DA re~ched significance at day 8th of :reatment and were maximal at day 15th. The Vmax of the enzyme started to increa,~;e at day 15th and was further ncreased at day 21st. After 21 clays of imipramine treatment, when adenylate cyclase Vmax was maximally increased, we found that the mmber of opiate binding sites as well as the inhibitory activity of DADLE and DynorphinH3 on adenylate cyclase ~,ere significantly decreased in the limbic areas. Fable 1 S,denylate cyclase (A.C.) activity and opiate binding in the limbic system of rats chronically treated witt,, imipramine. l'reatment
]aline [mipramine
Forskolin stimulated A.C. Vmax (Pmol/mg P/rain) 225.16±13.6 360.07+ 18.5 *
Kra (/tM)
3H'Bremazocine binding Bmax (Fmol/mg P)
4.35+0.8 5.42 + 0.9
244.97+16.7 167.10+ 12.4 * *
Kd (nM)
Dynorphin~.13 inhibited A.C. • of basal activity 0.1 laM 1/xM
IO/tM
0.30+0.07 0.40 + 0.08
82 94
70 79
"/2 81
p < 0.01; * * p < 0.05 with respect to control values. Data are the means :t:S.E. of at least four experiments performed in triplicate. The possibility that adenylate cyclase activity might control the number of membrane receptors coupled to the mzyme was tested in rats injected with cholera toxin in the caudate-putamen and in the limbic areas. Continuous lctivation of the enzyme by cholera toxin resul:ed in a signific~,nt ir~crease of D-: receptor number with no change in Lhe apparent affinity. The effect seemed to be restricted to the limbic areas. Studies are in progress to ascertain if :holera toxin treatment produces modifications in the number or affinity of opiate binding sites.
O.th.31.4 [
Utilization of N-ethyidiethanolamine (EDA) to eroduce an animal model of depression: effect of imipramine Freeman, J.J. and Looper Jr., J.E. College of Pharmacy. University of South Carolina, Columbia, SC 29208. U.S.A. " h e treatment proLocol is listed below in Table 1. Thirty-two male Sprague-Dawley rats were divided into 4 groups. -,,'oups 1 and 2 received pre-treatment testing in a water T-maze and all 4 groups were administered EDA in their :lrinldng wat~.r for 28 days. Subsequent to EDA treatment, all 4 groups received testing in a battery of tests for 18 days post-treatment. Group 4 received both EDA and imipramine treat ment (TCAD, 20 mg/kg i.p.) for 28 days. Both acquisition and decay were measured in a water T-maze as a measure of long-term memory (acquisition on days 1 and
Receptors modulation by chronic imipram~ne treatment De Montis, G.M., Devoto, P., Meloni, D., Saba~ P. and Tag!iamonte, A. Institute of Pharmacology and Biochemical Pathology, University of Cagliari, via Porceli 4. 09124 Cagliari. Italy Long term administration of imipramine to rats produced an increase of adenylate cyclase Vmax restricted to the imbic areas. This effect was prevented by the daily administration of a-methyl-p-tyrosine (a-MPT). associated to mipramine and given at a dose (50 mg/kg) which per s~ had no effect on adenylate cyclase activity. A time course of chronic imipramine effects on dopaminergic transmission in the limbic area showed that the tecrease of both D-i receptor number and adenylate cyclase stimulation by DA re~ched significance at day 8th of :reatment and were maximal at day 15th. The Vmax of the enzyme started to increa,~;e at day 15th and was further ncreased at day 21st. After 21 clays of imipramine treatment, when adenylate cyclase Vmax was maximally increased, we found that the mmber of opiate binding sites as well as the inhibitory activity of DADLE and DynorphinH3 on adenylate cyclase ~,ere significantly decreased in the limbic areas. Fable 1 S,denylate cyclase (A.C.) activity and opiate binding in the limbic system of rats chronically treated witt,, imipramine. l'reatment
]aline [mipramine
Forskolin stimulated A.C. Vmax (Pmol/mg P/rain) 225.16±13.6 360.07+ 18.5 *
Kra (/tM)
3H'Bremazocine binding Bmax (Fmol/mg P)
4.35+0.8 5.42 + 0.9
244.97+16.7 167.10+ 12.4 * *
Kd (nM)
Dynorphin~.13 inhibited A.C. • of basal activity 0.1 laM 1/xM
IO/tM
0.30+0.07 0.40 + 0.08
82 94
70 79
"/2 81
p < 0.01; * * p < 0.05 with respect to control values. Data are the means :t:S.E. of at least four experiments performed in triplicate. The possibility that adenylate cyclase activity might control the number of membrane receptors coupled to the mzyme was tested in rats injected with cholera toxin in the caudate-putamen and in the limbic areas. Continuous lctivation of the enzyme by cholera toxin resul:ed in a signific~,nt ir~crease of D-: receptor number with no change in Lhe apparent affinity. The effect seemed to be restricted to the limbic areas. Studies are in progress to ascertain if :holera toxin treatment produces modifications in the number or affinity of opiate binding sites.
O.th.31.4 [
Utilization of N-ethyidiethanolamine (EDA) to eroduce an animal model of depression: effect of imipramine Freeman, J.J. and Looper Jr., J.E. College of Pharmacy. University of South Carolina, Columbia, SC 29208. U.S.A. " h e treatment proLocol is listed below in Table 1. Thirty-two male Sprague-Dawley rats were divided into 4 groups. -,,'oups 1 and 2 received pre-treatment testing in a water T-maze and all 4 groups were administered EDA in their :lrinldng wat~.r for 28 days. Subsequent to EDA treatment, all 4 groups received testing in a battery of tests for 18 days post-treatment. Group 4 received both EDA and imipramine treat ment (TCAD, 20 mg/kg i.p.) for 28 days. Both acquisition and decay were measured in a water T-maze as a measure of long-term memory (acquisition on days 1 and