Possible influences on behavioral measures were tested in the elevated plus maze, spontaneous locomotor activity, and rotarod test, which are considered primarily predictive of the anxiolytic, sedative, and ataxic influence of BZs, respectively. The results confirmed the substantially diminished ataxic potential of BZ site agonists devoid of alpha(1) subunit-mediated effects,

with preserved anti-anxiety effects at 30 mg/kg of SH-053-S-CH3 and SH-053-S-CH3-2′F. However, all three ligands, dosed at 30 mg/kg, decreased spontaneous locomotor activity, suggesting that sedation may be partly dependent on activity mediated by alpha(5)-containing GABAA receptors. Hence, it could be of importance selleck compound to avoid substantial agonist activity at alpha(5) receptors by candidate anxioselective anxiolytics, if clinical sedation is to be avoided.”
“The medial preoptic area (MPOA) of the hypothalamus is critically involved in the regulation of male sexual behavior and has been implicated in several homeostatic processes. Serotonin (5-hydroxytryptamine, 5-HT) inhibits sexual behavior via effects in the MPOA, where there are high densities of 5-HT1A and 5-HT1B receptor subtypes. We used whole-cell recordings under voltage-clamp conditions to investigate the serotonergic modulation of

gamma-aminobutyric acid (GABA)ergic and glutamatergic synaptic Selleckchem AZD3965 transmission in mechanically dissociated rat MPOA neurons with native presynaptic nerve

endings. Spontaneous GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in the MPOA were completely blocked by bicuculline. Serotonin reversibly reduced the GABAergic mIPSC frequency without affecting the mean current amplitude. Serotonergic inhibition of mIPSC frequency was mimicked by (+/-)-8-hydroxy-2-dipropylaminotetralin hydrobromide, a specific 5-HT1A receptor agonist, and blocked by 1-(2- methoxyphenyl)-4-[4-(2-phthalimido)-butyl] Selleck Vorinostat piperazine hydrobromide, a specific 5-HT1A receptor antagonist. 6-Cyano-7-nitroquinoxaline-2,3-dione completely blocked spontaneous glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in the MPOA. Serotonin reversibly decreased the glutamatergic mEPSC frequency without affecting the mean current amplitude. Serotonergic inhibition of mEPSC frequency was mimicked by CGS 12066B, a specific 5-HT1B receptor agonist, and blocked by SB 216641, a specific 5-HT1B receptor antagonist. Stimulation of adenylyl cyclase with forskolin increased the frequencies of GABAergic mIPSCs and glutamatergic mEPSCs, and blocked the inhibitory effects of 5-HT. H-89, a selective protein kinase A (PKA) inhibitor, decreased the frequencies of GABAergic mIPSCs and glutamatergic mEPSCs, and blocked their reduction by 5-HT.