Modeling panic attacks.

The isomorphism of dorsal periaqueductal gray-evoked defensive behaviors and panic attacks was appraised in the present study. Thresholds of electrically induced immobility, trotting, galloping, jumping, exophthalmus, micturition and defecation were recorded before and after acute injections of anxiolytic, anxiogenic and antidepressant drugs. Antidepressant effects were further assessed 24h after injections of 7-14- and 21-day treatments. Chronic administration of clomipramine (CLM, 5-10mg/kg) a clinically effective antipanic drug increased the thresholds of immobility (24%), trotting (138%) galloping (75%), jumping (45%) and micturition (85%). The 21-day treatment with fluoxetine (FLX, 1mg/kg) virtually abolished galloping without changing the remaining responses. Galloping thresholds were also increased by 5mg/kg acute injections of CLM (19%) and FLX (25%). In contrast, chronically administered maprotiline (10mg/kg), a noradrenaline (NE) selective reuptake inhibitor, selectively increased the thresholds of immobility (118%). Diazepam (1.8mg/kg) and midazolam (MDZ, 2.5mg/kg) failed in attenuating the somatic defensive responses. Yet, the sedative dose of MDZ (5mg/kg) attenuated immobility. The panicogenic drug, pentylenetetrazole (50mg/kg), markedly decreased the thresholds of galloping (-51%) and micturition (-66%). These results suggest that whereas immobility is a NE-mediated attentional response, galloping is the panic-like behavior best candidate.

L-type calcium channels selectively control the defensive behaviors induced by electrical stimulation of dorsal periaqueductal gray and overlying collicular layers.

The present study reports the involvement of L-type calcium channels in the control of defensive behaviors produced by electrical stimulation of dorsal periaqueductal gray and overlying collicular layers. Rats that had chemitrodes in the dorsal midbrain and which stimulation produced freezing or flight behaviors with less than 55 microA were selected for drug experiments. Stimulation was repeated the day after the screening session 20 min following the microinjection into the dorsal periaqueductal gray of 15 nmol of either verapamil, a selective L-type calcium channel antagonist, or cobalt chloride (CoCl(2)), a calcium-specific channel modulator. Post-drug sessions were performed 48 h after. Threshold functions were obtained by logistic fitting of accumulated response frequencies. Verapamil and CoCl(2) significantly attenuated the output of immobility, exophthalmus, running and jumping. Although to a lesser degree, verapamil also attenuated defecation. Because CoCl(2) had no effect on defecation, the attenuation of this response by verapamil suggests a non-specific action of this drug. Neither verapamil nor CoCl(2) changed the output of micturition. Finally, whereas there was a complete recovery of defensive thresholds following the microinjection of verapamil, the attenuating effects of CoCl(2) were still present 48 h after. These results support an important role of L-type calcium channels in the neurogenesis of dorsal periaqueductal gray-evoked immobility, exophthalmus, running and jumping, but not defecation and micturition responses.

Thresholds of electrically induced defence reaction of the rat: short- and long-term adaptation mechanisms.

The thresholds of electrically induced defence reaction of the rat were studied through the logistic fitting of the response output. When stepwise increasing stimuli were applied at the dorsal midbrain, hierarchically organized mean thresholds, spaced 10 microA apart, were observed for immobility, running and jumping defensive behaviours. The parallel threshold functions of these responses, ranked in the above order, denote that they have distinct output probabilities when induced with sequential stepwise increasing stimuli. In contrast, when single daily stimuli were given in a random order, virtually superimposed threshold functions were obtained for these defensive behaviours. In this case, since the same output probabilities would be expected for immobility, running and jumping behaviours, the defence system seems to operate in a state of maximum entropy. The above data suggest that the dorsal midbrain, including the deep collicular layers and the periaqueductal gray, may encode hierarchical or non-hierarchical defensive patterns which, respectively, mimic either the attentive behaviour of the prey watching the approaching predator or its chaotic behaviour when cornered by a sudden attack. On the other hand, whereas quite stable thresholds were observed for the somatic defensive responses when 5 stimulation sessions were repeated over 15 days, the defecation and micturition output underwent a marked and progressive lessening. Since these autonomic responses have long been considered as reliable indexes of fear, their attenuation throughout the repeated sessions could express the rat adaptation to fear by the recurrence of the aversive experience. Taken together, these data suggest that while short-term neuronal adaptation could be responsible for the hierarchical threshold structure of the short interval stepwise stimulation, long-term neuronal adaptation could underlie the selective decrease of defecation and micturition responses over repeated sessions of intracranial stimulation.