Ejaculations induced by p-chloroamphetamine in the rat

Abstract

The ejaculatory response following acute injections of p-chloroamphetamine (PCA) and several other drugs was measured by weighing the compact seminal material accumulated over 2 hr. p-Chloroarnphetamine caused a dose-dependent ejaculatory response that was inhibited by the inhibitor of the synthesis of 5-hydroxytryptamine (5-HT), p-chlorophenylalanine (PCPA), neurotoxic doses of PCA, reserpine, DSP 4 a selective noradrenergic neurotoxin given 48 hr before PCA, the inhibitor of synthesis of noradrenaline (NA) FLA 63, the specific inhibitors of uptake of 5-HT, alaproclate, fluoxetine and norzimeldine and the selective inhibitor of the uptake of NA, CPP 199, the E form of norzimeldine. The doses of several receptor antagonists producing a 50% decrease in the weight of seminal material were determined. The non-selective 5-HT receptor antagonists, metitepine and methergoline, the selective α 1-adrenoreceptor antagonists, prazosin and phenoxybenzamine and the non-selective α-adrenoreceptor antagonist, phentolamine, had strong effects, followed by the selective 5-HT 2 antagonists, ketanserin and pirenperone. Yohimbine, an α 2-adrenoreceptor antagonist and atropine, a muscarinic receptor antagonist, only produced a partial blockade. The rank order of potency for some dopamine (DA) receptor antagonists was chlorpromazine, domperidone, haloperidol, pimozide. Remoxipride, a selective DA 2 receptor antagonist and the selective DA 1 antagonist, Sch 23390, had no effect. The following drugs had no effect: propranolol, naloxone, picrotoxin, cimetidine and mepyramine. The 5-HT receptor agonist 5-methoxy- N, N-dimethyltryptamine (5-MeODMT 3 mg/kg, i.p.) produced a small effect on the weight of seminal material, although 72% of the rats ejaculated. d-Amphetamine did not induce ejaculation at 5 mg/kg but had a marked effect at 15 mg/kg. The combination of 5-MeODMT (1 mg/kg, i.p.) and d-amphetamine (5 mg/kg, i.p.) caused a marked increase in the weight of seminal material. 8-Hydroxy-2-(di- n-propylamino)tetralin (8-OHDPAT), a very specific 5-HT receptor agonist, induced no ejaculation, either by itself or in combination with d-amphetamine. Also, apomorphine, a DA-agonist, failed to give a positive ejaculatory response. This result did not change when apomorphine was given together with 5-MeODMT or 5-MeODMT and clonidine an adrenoreceptor agonist. On the contrary, apomorphine and the combination of apomorphine and clonidine blocked the ejaculation induced by 5-MeODMT. The present data suggest that 5-HT plays a central role in the PCA-induced ejaculatory response in the rat. A noradrenergic input, probably peripheral, is necessary for a complete response.