Reduction of guinea pig pup isolation calls by anxiolytic and antidepressant drugs

Abstract

Guinea pigs possess central 5-HT1D receptors similar to humans but different from rats and mice. In order to study the role of this receptor on animal behaviour, it may be of interest to develop a paradigm measuring affective states in the guinea pig. Therefore we assessed the effects of a variety of psychotropic drugs on guinea pig pup isolation calls. Anxiolytic compounds such as the benzodiazepine receptor agonists diazepam and alprazolam, the full 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan, and alcohol reduced isolation calling by the guinea pig pup. Moreover, mixed antidepressant/anxiolytic compounds like the 5-HT uptake inhibitors fluvoxamine and clomipramine or the MAO-inhibitor clorgyline as well as the antidepressant NA uptake inhibitors desipramine and maprotiline suppressed vocalizations. The 5-HT1D/1A receptor agonist 5-CT was also very effective in reducing separation calls. Remarkably, the partial 5-HT1A receptor agonists buspirone and BMY 7378 did not affect calling. The neuroleptic haloperidol, the psychostimulant d-amphetamine, the putative anxiogenics DMCM and m-CPP and the putative anxiolytics ondansetron and CI-988 had no effect on isolation calls of guinea pig pups. We propose this paradigm could be helpful to assess behavioural effects of anxiolytic and antidepressant drugs in a species different from rat or mouse, and in which the effects of 5-HT1D receptor ligands may possibly be established.

Neurokinin1 Antagonists Potentiate Antidepressant Properties of Serotonin Reuptake Inhibitors, Yet Blunt Their Anxiogenic Actions: A Neurochemical, Electrophysiological, and Behavioral Characterization

“…Curiously, actions of NK 1 antagonists have not, as yet been documented. In fact, periaqueductal grey administration of substance P reduced USVs elicited by isolation in rats (Bassi et al, 2007), but NK 1 antagonists suppress isolation-induced (nonultrasonic) vocalizations in juveniles via actions in the amygdala (Molewijk et al, 1996;Rupniak et al, 2000;Brocco et al, 2008). This observation is coherent with the present finding that GR205171 attenuates stress-induced USVs.…”

“…This model is sensitive to SSRIs and, accordingly, citalopram reduced USVs (Molewijk et al, 1996;Sanchez and Meier, 1997;Millan et al, 2001a;Sánchez, 2003). Curiously, actions of NK 1 antagonists have not, as yet been documented.…”

The Gerbil Elevated Plus-Maze I Behavioral Characterization and Pharmacological Validation

“…Similarly, fluoxetine and paroxetine did not exhibit any anxiolyticlike activity in rat and mouse elevated plus-maze, and in fact produced anxiogenic effects (Silva et al 1999;Kurt et al 2000;Silva and Brandao 2000;Koks et al 2001). However, in contrast to the data generated in rat and mouse elevated plus-mazes, imipramine, fluoxetine, and paroxetine have been shown to produce anxiolytic-like actions in a number of other animal models of anxiety, including rat social interaction (Lightowler et al 1994), shock-or separation-induced vocalizations in rats and guinea pigs (Molewijk et al 1995;Molewijk et al 1996;Kramer et al 1998;Schreiber et al 1998;Podhorna and Brown 2000), and the four-plate test in mice (Hascoet et al 2000). Therefore, it is of interest that the gerbil elevated plus-maze appears to corroborate the anxiolytic findings with antidepressants in other invivo anxiety models and the recent findings in human patients.…”

Bombesin Receptors as a Novel Anti-Anxiety Therapeutic Target: BB1Receptor Actions on Anxiety through Alterations of Serotonin Activity

“…Specifically, we assessed the influence of systemic administration of PD 176252 [3-(1 H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)cyclohexylmethyl]-2-methyl-2-[3-(nitrophenyl)ureido]propionamide], a nonpeptide antagonist of the BB 1 receptor (with modest effects on BB 2 receptors) (Ashwood et al, 1998), on anxiety-like behaviors in ethologically relevant tests, including social interaction (File, 1980), approach to a familiar palatable snack in a novel (anxiogenic) environment , and in the guinea pig pup vocalization test (Molewijk et al, 1996). Effects of PD 176252 on fear-potentiated startle were also assessed to determine the impact on learned fear responses (Lee and Davis, 1997).…”