Cooper, R.L. *; Tabor, J; Chase, R.J.: Altered responsiveness to 5-HT at the crayfish neuromuscular junction: receptor up- & down-regulation

Serotonin (5-HT)levels in the hemolymph of crustaceans has been implied to alter the assertiveness and aggression during social interactions (Huber et al., 1997; Sneddon et al., 2000). Pharmacological examination shows that m-CPP has agonistic functions in crayfish altering sensory drive into the animals ventral nerve cord (Yeh et al., 1996), thus suggesting the presence of one or both 5-HT1 and 5-HT2 receptor types. Based on evidence in other systems, one would suspect that chronically sustained 5-HT levels would results in a compensatory negative feed-back regulation and/or that target tissues would diminish their sensitivity to high levels of circulating free 5-HT. Altered cellular activity as well the action of agonists or antagonists being bound to a receptor can induce regulation in the levels of functional receptors (Welner et al., 1989; Kokay and Mercer, 1997; Fone et al., 1998). For example it has been shown that 5-HT1A receptors will demonstrate desensitization when either an agonist or antagonist is present (Hensler and Truett, 1998). The purpose of our study is to address the issue of up- and down-regulation in the sensitivity of the responsiveness to exogenously applied 5-HT at the neuromuscular junctions (NMJs) of crayfish in which the animals have had either reduced endogenous 5-HT levels by enzymatic inhibition in the synthesis of 5-HT or have had a chronic presence of an agonist in their hemolymph. Injections of the 5-HT1 and 5-HT2 vertebrate receptor agonist, m-CPP, for 1 week resulted in a decreased responsiveness to 5-HT. The reduction of systemic 5-HT by injections of p-CPA, which blocks the synthesis of 5-HT, resulted in a supersensitivity of both tonic and phasic NMJs.Funding: NSF grants IBN-9808631 (RLC) & NSF-ILI-DUE 9850907 (RLC).