Pharmacology, biochemistry, and behavior
-
Pharmacol. Biochem. Behav. · Jul 2014
5-HT1A receptor activation reduces fear-related behavior following social defeat in Syrian hamsters.
Social defeat leads to selective avoidance of familiar opponents as well as general avoidance of novel, non-threatening intruders. Avoidance of familiar opponents represents a fear-related memory whereas generalized social avoidance indicates anxiety-like behavior. We have previously shown that serotonin signaling alters responses to social defeat in Syrian hamsters, although it is unclear whether serotonin modulates defeat-induced fear, anxiety, or both. ⋯ Social defeat increased the number of Arc immunopositive cells in the central amygdala (CeA), prelimbic cortex (PL), and BLA, and 8-OH-DPAT treatment reduced Arc immunoreactivity in the PL. These results suggest that 5-HT1A receptor activation impairs the fear memory associated with social defeat, but does not alter defeat-induced anxiety. Overall, 5-HT1A receptor activation may impair Arc expression in select brain regions such as the PL and thereby disrupt the development of a fear memory essential for the conditioned defeat response.
-
Pharmacol. Biochem. Behav. · Jul 2014
Intrathecal injection of selected peptide Myr-RC-13 attenuates bone cancer pain by inhibiting KIF17 and NR2B expression.
Although bone cancer pain is a common intractable clinical symptom, its underlying mechanisms are still elusive. Accumulating evidence reveals that the N-methyl-D-aspartate (NMDA) receptor containing a 2B subunit (NR2B) in the spinal cord contributes to bone cancer pain. Our preliminary study demonstrated that intrathecal injection of fusion peptide Myr-RC-13 could disrupt spinal KIF17/mLin10 interaction, which is an essential component of KIF17-mediated NR2B transport. ⋯ In addition, repetitive spinal delivery of Myr-RC-13 relieved bone cancer-related mechanical allodynia and spontaneous pain behaviors, and down-regulated expression of spinal KIF17 and NR2B. Finally, our results demonstrated that selected peptide Myr-RC-13 was able to attenuate bone cancer pain via decreasing spinal KIF17 and NR2B expressions. Therefore, selected peptide Myr-RC-13 might be a potential analgesic strategy for bone cancer pain.
-
Most of the available antidepressant medications, including tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and dual noradrenergic/serotonergic reuptake inhibitors have been reported to be associated with sexual dysfunction in both sexes. This manuscript reviews evidence concerning the relative incidence of treatment emergent sexual dysfunction in men being treated with antidepressant drugs. Both double-blind controlled trials and large clinical series report a high incidence of sexual dysfunction, especially ejaculatory delay, with serotonergic drugs. The incidence of sexual dysfunction in men appears to be much lower with drugs whose primary mechanism of action involves adrenergic or dopaminergic systems.
-
Pharmacol. Biochem. Behav. · Jun 2014
ReviewAntidepressant-related sexual dysfunction - perspectives from neuroimaging.
Sexual dysfunction is not only a common symptom in major depression but also a frequent side-effect of antidepressant medication, mainly of the selective serotonin reuptake-inhibitors (SSRI) that are often prescribed as a first line treatment option. Despite of the increasing incidence and prescription rates, neuronal mechanisms underlying SSRI-related sexual dysfunction are poorly understood and investigations on this topic are scarce. ⋯ This review summarizes the recent literature regarding the basic clinical findings and imaging correlates of antidepressant-related sexual dysfunction linking brain regions and networks potentially involved to phases and subcomponents of sexual processing and antidepressant action. In particular, fMRI studies on SSRI antidepressants including paroxetine and SNRIs including bupropion are highlighted.
-
Pharmacol. Biochem. Behav. · Jun 2014
ReviewSexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release?
Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. ⋯ Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling.