RT Journal Article
SR Electronic
T1 Regionally specific neural adaptation of beta adrenergic and 5-hydroxytryptamine2 receptors after antidepressant administration in the forced swim test and after chronic antidepressant drug treatment.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 956
OP 962
VO 246
IS 3
A1 I A Paul
A1 G E Duncan
A1 K R Powell
A1 R A Mueller
A1 J S Hong
A1 G R Breese
YR 1988
UL http://jpet.aspetjournals.org/content/246/3/956.abstract
AB In the present investigation, experiments were performed in order to determine whether antidepressants are capable of inducing regionally specific adaptation of beta adrenergic and 5-hydroxytryptamine2 (5-HT2) receptors after chronic administration or when combined with the forced swim test. The drugs tested were imipramine, amitriptyline, pargyline and nomifensine. The regional pattern of beta adrenergic or 5-HT2 receptor binding changes induced after chronic treatment with these antidepressants was not uniform. All of the drugs reduced [3H]dihydroalprenolol binding to cortical membranes after chronic treatment but only two, imipramine and pargyline, did so in hippocampus. All of the antidepressants reduced cortical, but not hippocampal, beta adrenergic receptor binding after 2 days of treatment, indicating that the rate of antidepressant-induced neural adaptation is regionally specific. All of the drugs, except nomifensine, induced down regulation of both cortical and hippocampal 5-HT2 receptors after chronic treatment, as measured by [3H]ketanserin binding. The forced swim test accelerated the reduction of [3H] dihydroalprenolol binding in hippocampus induced by imipramine and pargyline while producing no further effect on cortical beta adrenergic receptors. The down-regulation of hippocampal, but not cortical 5-HT2 receptors by imipramine and pargyline was also facilitated in rats processed in the forced swim test. These results provide further support for the view that the forced swim antidepressant drug screen may be of heuristic value as a model of the adaptive neural mechanisms that accompany chronic antidepressant drug treatment. Furthermore, these data provide evidence that multiple neural mechanisms may be involved in the adaptive changes after antidepressant drug treatment.