Nicotinic receptors

Regulation of normal or abnormal behaviour is critically controlled by the central serotonergic systems. Recent evidence has suggested that serotonin (5-HT) neurotransmission dysfunction contributes to a variety of pathological conditions, including depression, anxiety, schizophrenia and Parkinson’s disorders. There is also a great amount of evidence indicating that 5-HT signalling may affect the reinforcing properties of drugs of abuse by the interaction and modulation of dopamine (DA) function. This chapter is focused on one of the more addictive drugs, nicotine. It is widely recognised that the effects of nicotine are strongly associated with the stimulatory action it exhibits on mesolimbic DAergic function. We outline the role of 5-HT and its plethora of receptors, focusing on 5-HT2 subtypes with relation to their involvement in the neurobiology of nicotine addiction. We also explore the novel pharmacological approaches using 5-HT agents for the treatment of nicotine dependence. Compelling evidence shows that 5-HT2C receptor agonists may be possible therapeutic targets for smoking cessation, although further investigation is required.peer-reviewe

Facilitation and inhibition of male rat ejaculatory behaviour by the respective 5-HT(1A) and 5-HT(1B) receptor agonists 8-OH-DPAT and anpirtoline, as evidenced by use of the corresponding new and selective receptor antagonists NAD-299 and NAS-181

1. Ejaculatory problems and anorgasmia are well-known side-effects of the SSRI antidepressants, and a pharmacologically induced increase in serotonergic neurotransmission inhibits ejaculatory behaviour in the rat. In the present study the role of 5-HT(1A) and 5-HT(1B) receptors in the mediation of male rat ejaculatory behaviour was examined by use of selective agonists and antagonists acting at these 5-HT receptor subtypes. 2. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.25–4.00 μmol kg(−1) s.c.) produced an expected facilitation of the male rat ejaculatory behaviour, and this effect was fully antagonized by pretreatment with the new selective 5-HT(1A) receptor antagonist (R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide hydrogen (2R,3R) tartrate monohydrate (NAD-299) (1.0 μmol kg(−1) s.c.). NAD-299 by itself (0.75–3.00 μmol kg(−1) s.c.) did not affect the male rat ejaculatory behaviour. 3. The 5-HT(1B) receptor agonist anpirtoline (0.25–4.00 μmol kg(−1) s.c.) produced a dose-dependent inhibition of the male rat ejaculatory behaviour, and this effect was fully antagonized by pretreatment with the 5-HT(1B) receptor antagonist isamoltane (16 μmol kg(−1) s.c.) as well as by the new and selective antagonist (R)-(+)-2-(3-morpholinomethyl-2H-chromene-8-yl)oxymethylmorpholino methansulphonate (NAS-181) (16 μmol kg(−1) s.c.). Isamoltane (1.0–16.0 μmol kg(−1) s.c.) and NAD-181 (1.0–16.0 μmol kg(−1) s.c.) had no, or weakly facilitatory effects on the male rat ejaculatory behaviour. The non-selective 5-HT(1) receptor antagonist (−)-pindolol (8 μmol kg(−1) s.c.), did not antagonize the inhibition produced by anpirtoline. 4. The present results demonstrate opposite effects, facilitation and inhibition, of male rat ejaculatory behaviour by stimulation of 5-HT(1A) and 5-HT(1B) receptors, respectively, suggesting that the SSRI-induced inhibition of male ejaculatory dysfunction is due to 5-HT(1B) receptor stimulation