Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors

Activation of 5-HT1A receptors in the dorsal periaqueductal gray (dPAG) impairs escape behavior, suggesting a panicolytic-like effect. Cannabidiol (CBD), a major non-psychotomimetic compound present in Cannabis sativa, causes anxiolytic-like effects after intra-dPAG microinjections by activating 5-HT1A receptors. In the present work we tested the hypothesis that CBD could also impair escape responses evoked by two proposed animal models of panic: the elevated T-maze (ETM) and electric stimulation of dPAG. In experiment 1 male Wistar rats with a single cannula implanted in the dPAG received a microinjection of CBD or vehicle and, 10 min later, were submitted to the ETM and open field tests. In experiment 2 escape electrical threshold was measured in rats with chemitrodes implanted in the dPAG before and 10 min after CBD microinjection. In experiment 3 similar to experiment 2 except that the animals received a previous intra-dPAG administration of WAY-100635, a 5-HT1A receptor antagonist, before CBD treatment. In the ETM microinjection of CBD into the dPAG impaired inhibitory avoidance acquisition, an anxiolytic-like effect, and inhibited escape response, a panicolytic-like effect. The drug also increased escape electrical threshold, an effect that was prevented by WAY-100635. Together, the results suggest that CBD causes panicolytic effects in the dPAG by activating 5-HT1A receptors. (C) 2010 Elsevier B.V. All rights reserved.

GABAergic antagonist blocks the reduction of tonic immobility behavior induced by activation of 5-HT(2) receptors in the basolateral nucleus of the amygdala in guinea pigs

Tonic immobility (TI) is a temporary state of profound motor inhibition induced by situations that generate intense fear, with the objective of protecting an animal from attacks by predators. A preliminary study by our group demonstrated that microinjection into the basolateral nucleus of the amygdala (BLA) of an agonist to 5-HT(1A) and 5-HT(2) receptors promoted a decrease in TI duration. In the current study, the effects of GABAergic stimulation of the BLA and the possible interaction between GABA(A) and 5-HT(2) receptors on TI modulation were investigated. Observation revealed that GABAergic agonist muscimol (0.26 nmol) reduced the duration of TI episodes, while microinjection of the GABAergic antagonist bicuculline (1 nmol) increased TI duration. Additionally, microinjection of 5-HT(2) agonist receptors (alpha-methyl-5-HT, 0.32 nmol) into the BLA decreased TI duration, an effect reversed by pretreatment with bicuculline (at the dose that had no effect per se, 0.2 nmol). Moreover, the activation of GABA(A) and 5-HT(2) receptors in the BLA did not alter the spontaneous motor activity in the open field test. These experiments demonstrated that the activation of GABA(A) and 5-HT(2) receptors of the BLA possibly produce a reduction in unconditioned fear that decreases the TI duration in guinea pigs, but this is not due to increased spontaneous motor activity, which could affect a TI episode nonspecifically. Furthermore, these results suggest an interaction between GABAergic and serotoninergic mechanisms mediated by GABA(A) and 5-HT(2) receptors. In addition, the GABAergic circuit of the BLA presents a tonic inhibitory influence on TI duration. (C) 2009 Elsevier Inc. All rights reserved.

Communicating trustworthiness and building trust in interorganizational virtual organizations

We propose a theory of trust in interorganizational virtual organizations that focuses on how trustworthiness can be communicated and trust built in this environment. The theory highlights three issues that must be dealt with if the potential obstacles to the development of trust in the virtual context are to be overcome. These are communication of trustworthiness facilitated by reliable Information and Communication Technology (ICT), establishment of a common business understanding, and strong business ethics. We propose four specific propositions relating to these issues, and suggest topics to be explored in future research. (C) 2001 Elsevier Science Inc. All rights reserved.

The K5 gamble: National defence and nation building under the People's Republic of Kampuchea

The K5 Plan for the defence of the Cambodian-Thai border was the response of the People's Republic of Kampuchea and its Vietnamese mentors to the threat posed by the resistance forces, particularly the Khmer Rouge, to its efforts to rebuild the nation and consolidate its administration. The very real defence gains, however, were made at the cost of bitter popular resentment over the way those gains were made.