Preliminary Communication Repeated Treatment with Sa4503, a Selective Sigma1 Receptor Agonist, Up-regulates 1-adrenergic System. a Behavioral Study

SA4503 [1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride] has been described as a new, selective sigma ( ) receptor agonist with a potential antidepressant activity [8, 9, 17]. It has been reported that SA4503 shows an antidepressant-like activity in mice [8, 17]. Similar effects were observed after the administration of (+)-pentazocine (another receptor agonist) and DTG (a / agonist) to mice and rats. Moreover, those antidepressant-like effects were antagonized by the receptor antagonist, NE-100 [8, 9, 16, 17]. Our previous studies indicated that SA4503 decreased the immobility time in the forced swimming test in rats and showed a synergistic effect with imipramine in that model. When given repeatedly (14 or 21 days), SA4503 induced effects similar to those produced by many clinically active antidepressant drugs (ADs), e.g. it enhanced the D-amphetamineor quinpirole-induced hyperactivities in rats, and did not change the D-amphetamine stereotypy (in preparation). It was demonstrated that ADs administered repeatedly increased the responsiveness of the -adrenergic system (sensitivity of postsynaptic -adrenergic receptors) at both behavioral and biochemical levels (e.g. they increased the clonidine-induced Polish Journal of Pharmacology ! "#$ % ! &'