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Drug-induced penile erections (PE) were initially suggested to be 5-HT1B receptor mediated. However, since the discovery of the 5-HT1C receptor a number of compounds, considered to be 5-HT1B selective, appear to bind more strongly to the 5-HT1C receptor and this prompted a re-evaluation of the receptor subtype involved in PE induction. PE could be induced by the 5-HT agonists mCPP (0.22-2.2 mg/kg), TFMPP (0.46-1.0 mg/kg) and MK 212 (0.1-1.0 mg/kg). The 5-HT agonist DOI (0.022-0.22 mg/kg) did not induce PE in placebo-pretreated rats but in rats pretreated with various 5-HT2 antagonists it did. These compounds have in common a strong affinity for the 5-HT1C receptor, mCPP (0.46 mg/kg)-induced PE could be antagonized by the 5-HT antagonists metergoline, cyproheptadine, mesulergine, mianserin, ritanserin and ketanserin. Their ED50S were 0.04, 0.4, 0.03, 0.06, 0.4 and 2 mg/kg, respectively. The potency of both the agonists to induce, and the antagonists to inhibit, PE was found to be dependent on their selectivity for the 5-HT1C receptor versus the 5-HT2 receptor. Spiperone (0.1-1.0 mg/kg) and GR 38032F (1-10 mg/kg) did not antagonise mCPP-induced PE. 8-OH-DPAT and 5MeODMT counteracted mCPP (0.46 mg/kg)-induced PE. Their ED50S were 0.03 and 0.4 mg/kg, respectively. DOI counteracted mCPP induced PE only at doses above 1 mg/kg, whereas CGS 12066B (1.0-10 mg/kg) was inactive. The results suggest that PE are induced by activation of the 5-HT1C receptor and are functionally inhibited by activation of 5-HT1A or 5-HT2 receptors.

Two experiments were conducted to determine the effects of the M1 muscarinic receptor antagonist pirenzepine on place navigation in a water maze. In the first experiment rats were required to learn the location of a hidden platform following intracerebroventricular injections of equimolar doses of pirenzepine or scopolamine methylbromide. Both drugs dose-dependently impaired spatial learning according to both escape latency data and transfer test analysis. Pirenzepine was approximately 3 times less potent than scopolamine, a potency ratio which suggests M1 receptor mediation of the impairment. In the second experiment pirenzepine (1 approximately 92.3 micrograms/rat ICV) was injected prior to training on a simultaneous place discrimination task in the water maze. Impairments of choice accuracy were found with a dose of 20 micrograms/rat in the absence of any marked increases in either errors of omission or choice latency. These data suggest that M1 receptor blockade impairs processes which are involved in spatial learning.

1 Different 5-hydroxytryptamine (5-HT) receptor subtypes mediate different behavioural responses. Compounds acting at more than one 5-HT receptor exert behavioural effects which may be the result of response competition or a specific interaction between pathways within the CNS. Therefore the mutual interaction between different 5-HT receptor subtypes was studied.2 Hypothermia and hypoactivity in mice induced by the 5-HTlA-agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) could be attenuated by the preferential 5-HT1c-agonists MK 212, 1-(meta-chlorophenyl)-piperazine (mCPP) and m-trifluoromethyl phenyl piperazine (TFMPP), and by the mixed 5-HT211c-agonist 1(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The mixed 5-HTIA/lB-agonist CGS 12066B at 10mg kg-1 potentiated hypothermia and had no effect on hypoactivity.3 Forepaw treading in rats induced by the 5-HTIA-agonist 8-OH-DPAT was attenuated by the 5-HT1c-agonists MK 212 and mCPP. The 5-HT1c-agonist TFMPP had a bimodal effect: at low doses (<1mgkg-1) it potentiated, and at higher doses (>2.2mgkg-1) it attenuated forepaw treading. the mixed 5-HT2/1c-agonist DOI produced 5-HT2-related behaviours and potentiated 8-OH-DPAT-induced forepaw treading. This indicates an attenuating effect of 5-HTic-receptor activation and a potentiating effect of 5-HT2-receptor activation. CGS 12066B had no effect in this respect. 4 Head shakes in rats induced by DOI could be attenuated by 8-OH-DPAT, TFMPP, mCPP and MK 212. The ID5os were 0.03, 0.7, 0.1 and 2mgkg 1, respectively. This suggests that a 5-HT2-receptor-mediated effect may be attenuated by activation of 5-HT1A-or 5-HT1c-receptors. CGS 12066B attenuated the head shake response but only at 10 mg kg-'. 5 The results suggest that interactions exist between the different 5-HT receptor subtype-mediated events. Therefore, care is needed in drawing conclusions from functional measurements when compounds have more or less equal affinities for more than one 5-HT-receptor subtype.