Biomedical subjects

L C Schenberg

Publications and source records attributed to L C Schenberg.

At least 19 recordsLinked to original sources

PubMed2001

Long-term effects of clomipramine and fluoxetine on dorsal periaqueductal grey-evoked innate defensive behaviours of the rat.

RATIONALE: The defensive responses induced by electrical stimulation of dorsal periaqueductal grey (DPAG) of the rat have been proposed as a model of panic attacks in humans. OBJECTIVE: The present experiments were carried out to evaluate the long-term effects of clinically effective panicolytics on these responses. METHODS: Rats that had electrodes implanted into the DPAG were treated for 21 days with clomipramine (CLM; 5, 10 and 20 mg/kg), fluoxetine (FLX; 1 and 5 mg/kg) or saline. Long-term effects were assessed prior to the treatment to avoid acute drug effects. Threshold logistic functions of defensive responses were compared by likelihood ratio coincidence tests. RESULTS: CLM attenuated DPAG-evoked defensive behaviours at a time-course similar to that observed in panic therapy. Administration of 10 mg/kg CLM for 21 days produced significant increases in the thresholds of immobility (24%), running (49%) and jumping (45%). Splitting of running into single responses disclosed selective threshold increases of galloping (75%) and trotting (138%) with 5 and 10 mg/kg, respectively. Thresholds of micturition were markedly increased (87%) by 5 mg/kg CLM. In turn, FLX (1 mg/kg) virtually abolished the galloping response. No threshold changes were observed following the long-term administration of the higher dose of either CLM or FLX. Saline-treated rats had a significant increase (35%) in galloping thresholds only. CONCLUSIONS: The present data partially validate the DPAG-evoked defence reaction of the rat as a model of panic attacks in humans. Attenuation of galloping by lower doses of FLX and CLM also suggests the prominent modulation of this response by serotonin.

Aggression↗

PubMed2001

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.

Animals↗

PubMed2001

The brain decade in debate: II. Panic or anxiety? From animal models to a neurobiological basis.

This article is a transcription of an electronic symposium sponsored by the Brazilian Society of Neuroscience and Behavior (SBNeC). Invited researchers from the European Union, North America and Brazil discussed two issues on anxiety, namely whether panic is a very intense anxiety or something else, and what aspects of clinical anxiety are reproduced by animal models. Concerning the first issue, most participants agreed that generalized anxiety and panic disorder are different on the basis of clinical manifestations, drug response and animal models. Also, underlying brain structures, neurotransmitter modulation and hormonal changes seem to involve important differences. It is also common knowledge that existing animal models generate different types of fear/anxiety. A challenge for future research is to establish a good correlation between animal models and nosological classification.

Anti-Anxiety Agents↗

PubMed2001

The brain decade in debate: III. Neurobiology of emotion.

This article is a transcription of an electronic symposium in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the neurobiology of emotion. Four basic questions were debated: 1) What are the most critical issues/questions in the neurobiology of emotion? 2) What do we know for certain about brain processes involved in emotion and what is controversial? 3) What kinds of research are needed to resolve these controversial issues? 4) What is the relationship between learning, memory and emotion? The focus was on the existence of different neural systems for different emotions and the nature of the neural coding for the emotional states. Is emotion the result of the interaction of different brain regions such as the amygdala, the nucleus accumbens, or the periaqueductal gray matter or is it an emergent property of the whole brain neural network? The relationship between unlearned and learned emotions was also discussed. Are the circuits of the former the underpinnings of the latter? It was pointed out that much of what we know about emotions refers to aversively motivated behaviors, like fear and anxiety. Appetitive emotions should attract much interest in the future. The learning and memory relationship with emotions was also discussed in terms of conditioned and unconditioned stimuli, innate and learned fear, contextual cues inducing emotional states, implicit memory and the property of using this term for animal memories. In a general way it could be said that learning modifies the neural circuits through which emotional responses are expressed.

Amygdala↗

PubMed2000

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.

Aggression↗

PubMed2000

Micturition and defensive behaviors are controlled by distinct neural networks within the dorsal periaqueductal gray and deep gray layer of the superior colliculus of the rat.

Electrical stimulation of the dorsal periaqueductal gray (DPAG) or the deep gray layer of the superior colliculus (DGSC) of rats placed in an open-field elicited either a display of tense immobility, accompanied by exophthalmus and/or defecation and micturition, or running and jumping responses. Threshold curves of each response were obtained for each structure by the logistic fitting of accumulated response frequencies. DPAG and DGSC threshold curves were compared by likelihood-ratio coincidence tests. The output of micturition was significantly higher following the stimulation of DPAG (P < 0.0005). In contrast, no differences were found for the remaining responses. These data support previous studies in anaesthetized cats suggesting the critical involvement of DPAG in the control of micturition. Furthermore, they also suggest that topographically distinct neural networks within the DPAG and DGSC control micturition and the other defensive behaviors.

Animals↗

PubMed1999

Cardiovascular changes following acute and chronic chemical lesions of the dorsal periaqueductal gray in conscious rats.

This study was carried out to investigate the effects of chemical lesions of dorsal periaqueductal gray (DPAG) on resting arterial pressure (AP) and heart rate (HR) as well as on cardiac baroreflex of conscious normotensive rats. Lesions were performed by bilateral microinjections of 150 mM NMDA into the DPAG (DPAG-lesion group). Controls were similarly injected with 165 mM NaCl (DPAG-sham group). Animals with chronic lesions confined only to the superior colliculus (SC-lesion group) were also used as controls of DPAG-lesion. Cardiovascular parameters were recorded 1 or 7 days after the microinjections of NMDA in acute and chronic groups, respectively. Cardiac baroreflex was assessed by measuring the HR responses to the intravenous injection of phenylephrine or sodium nitroprusside. Baroreflex was estimated by sigmoidal curve fitting of HR responses. An increased baroreflex gain was observed in chronic DPAG-lesion rats compared to both DPAG-sham (p < 0.01) and SC-lesion (p < 0.05) chronic groups. The chronic DPAG-lesion group showed also an elevation of both the tachycardia (p < 0.05) and bradycardia (p < 0.01) plateaus compared to chronic DPAG-sham rats, while the SC-lesion group showed an elevation of the bradycardia plateau only (p < 0.01). Similar results on baroreflex function were observed following acute lesion of the DPAG, i.e. an increase in baroreflex gain (p < 0.01) and the elevation of both tachycardia (p < 0.05) and bradycardia plateaus (p < 0.01) compared to the acute DPAG-sham group. Resting AP and HR did not differ among the chronic groups. In contrast, the acute lesion of the DPAG produced a reduction in AP (p < 0.01) accompanied by an increase in HR (p < 0.01). The present data suggest that the DPAG is involved in the tonic and reflex control of AP and HR in conscious rats. In addition, the SC seems to contribute to the baroreflex cardioinhibition.

Adrenergic alpha-Agonists↗

PubMed1998

NMDA-coupled periaqueductal gray glycine receptors modulate anxioselective drug effects on plus-maze performance.

The present study was carried out to investigate a possible interaction between the effects of anxiety modulating drugs which act at the GABA-A receptor complex and selective N-methyl-D-aspartic acid (NMDA) coupled glycine receptor (GLY-B receptor) ligands within the dorsal periaqueductal gray (DPAG). The plus-maze performance of rats pretreated with diazepam (0.37 and 0.75 mg/kg, i.p.) or pentylenetetrazole (15 and 30 mg/kg, i.p.), standard anxiolytic and anxiogenic drugs respectively, was assessed following intra-periaqueductal injections of either glycine (0.2 M, 0.4 microl/30 s, i.c.) or its competitive antagonist, 7-chlorokynurenic acid (7ClKYN, 0.02 M, 0.4 microl/30 s, i.c.). Whilst diazepam produced a typical anxiolytic effect in intracranially-injected CSF rats, increasing open arm exploration, pentylenetetrazole displayed an opposite anxiogenic profile. Either anxiogenic or anxiolytic effects were seen in peripherally-injected vehicle rats following intra-periaqueductal injections of glycine or 7ClKYN, respectively. Intra-periaqueductal injection of glycine markedly attenuated the anxiolytic effect of diazepam. Moreover, while the anxiogenic effects of pentylenetetrazole were barely changed by glycine, they were markedly attenuated by intra-periaqueductal injection of 7ClKYN. Interaction of diazepam and 7ClKYN produced non-selective sedative-like effects which masked any possible anxiolytic action. Accordingly, the present results suggest that the NMDA-coupled glycine receptors located in the DPAG interfere with anxioselective effects of GABA-A acting drugs on the elevated plus-maze. In spite of the prevailing notion that the NMDA coupled glycine receptor is saturated at in vivo brain concentrations of glycine, our results also suggest that either unoccupied or low-affinity GLY-B receptors are likely to be activated by glycine injection into DPAG.

Animals↗

PubMed1997

Alcohol dependence induced in rats by semivoluntary intermittent intake.

The objective of the present experiment was to assess ethyl alcohol (ETOH) dependence brought about by a semivoluntary intermittent intake regimen in rats. Male Wistar rats weighing 150-250 g at the onset of the experiment were assigned to the following groups: 0% ETOH (N = 11), 5% ETOH (N = 20), 20% ETOH (N = 20) and 40% ETOH (N = 18). ETOH solutions were offered at the end of the day and overnight from Monday to Friday, and throughout weekends, for 90 days. The concentration of the ETOH solutions was increased in a stepwise fashion allowing the rats to get used to the taste of alcohol. Reposition of pure water was permitted during 1-h water drinking periods in the morning. Daily volume intake (+/- SEM) averaged 25.4 +/- 0.4 ml (0% ETOH), 23.8 +/- 0.6 ml (5% ETOH), 17.6 +/- 0.7 ml (20% ETOH) and 17.5 +/- 0.6 ml (40% ETOH). ETOH consumption differed significantly (P < 0.05) among groups, averaging 4.4 +/- 0.2 g kg-1 day-1 (5% ETOH), 10.3 +/- 0.3 g kg-1 day-1 (20% ETOH) and 26 +/- 1.2 kg-1 day-1 (40% ETOH). Furthermore, ETOH detection in plasma 10-12 h after offering the solution indicated that its consumption in the 40% ETOH group was sufficient to override its metabolism. Overt signs of ETOH dependence, such as increased thirst, hyperactivity, puffing, hair ruffling and startle responsiveness as well as reduced drowsiness, were significantly increased in the 20% and 40% ETOH groups compared to the 0% and 5% groups. Accordingly, the model described here proved to be a useful tool for the evaluation of subtle or moderate behavioral and physical consequences of long-term ETOH intake.

Alcohol Drinking↗

PubMed1995

Modulation of the cardiovascular defence response by low frequency stimulation of a deep somatic nerve in rats.

In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation in the dorsal part of the periaqueductal grey matter (PAG) produced a pressor response with tachycardia and vasodilatation in the hind limb, a pattern known as the 'cardiovascular defence reaction' owing to its resemblance to fear-induced hemodynamic changes. Following a 20-min period of stimulation of the peroneal nerve at 10 Hz with current intensities sufficient to recruit group II and III fibres the pressor component of the response was significantly reduced compared to control rats. The maximum decrease of the PAG-evoked pressor response was about 50% (from 32.0 +/- 0.7 to 16.6 +/- 5.9 mmHg). The effect lasted for between 60 and 290 min and was not correlated to baseline blood pressure changes observed after the stimulation of the nerve. In contrast, the tachycardia and hind limb vasodilator components of the defence response as well as their baseline values remained unchanged. Resting blood pressure did not change significantly in control rats but showed a small progressive increase in stimulated rats which reached significance 90-100 min after the stimulation. These results suggest that the afferent input from high threshold fibres in a muscle nerve can produce a selective and long-lasting depression of the vasoconstrictor components of the midbrain-evoked cardiovascular defence response. This effect is discussed in relation to the long-lasting sympathoinhibitory effects of acupuncture-like stimulation or sustained physical exercise.

Action Potentials↗

PubMed1995

Attenuation of the midbrain-evoked defense reaction by selective stimulation of medullary raphe neurons in rats.

In rats anesthetized with alfaxalone/alfadolone, electrical stimulation in the dorsal periaqueductal gray matter (PAG) evoked a cardiovascular defense reaction with increases in blood pressure, heart rate, femoral conductance, and respiratory activity but a decrease in renal conductance. These responses were attenuated significantly after microinjection of 200 nl 0.1 M DL-homocysteic acid (DLH) into nucleus raphe magnus (NRM, n = 12) or nucleus raphe obscurus (NRO, n = 22). The maximum reduction in the pressor response was similar after stimulation in NRM (-36.3%) and NRO (-37.3%). The reduction of the tachycardia, however, was greater after stimulation in NRM (-78.1%) compared with NRO (-34.6%). The maximum reduction in the PAG-evoked vasodilation of the hindlimb averaged -55.7% and -55.3% after stimulation of NRM and NRO, respectively, whereas the renal vasoconstriction was reduced by -66.4% and -79.0%. The PAG-evoked increase in respiratory amplitude was attenuated only after stimulation of NRO. It is concluded that neurons in NRM and NRO may be involved in modulating the level of excitability of neurons in the midbrain defense area and/or in its efferent pathway.

Animals↗

PubMed1995

Role of periaqueductal gray matter in hypertension in spontaneously hypertensive rats.

We performed experiments to study the effects of electrolytic lesions of periaqueductal gray matter on mean blood pressure, heart rate, and cardiac baroreflex in adult male spontaneously hypertensive rats. Cardiac baroreflex was assessed by the administration of randomly assigned doses of phenylephrine (0.3 to 5.0 micrograms/kg i.v.) or sodium nitroprusside (1.5 to 5.0 micrograms/kg i.v.) to unanesthetized rats. Bilateral lesions of the periaqueductal gray matter (0.5 mA/5 s) were then performed with rats under sodium pentobarbital anesthesia (35 mg/kg i.p.). Twenty hours after lesion, cardiac baroreflex was retested. Baroreflex data were analyzed by sigmoidal curve fitting. Lesion rats (n = 12) showed a significant decrease in both the gain (delta = -0.89 +/- 0.38 beats per minute [bpm]/mm Hg, P < .05) and curve midpoint (delta = -15 +/- 6 mm Hg, P < .05) of the cardiac baroreflex. Moreover, despite a moderate increase in heart rate (delta = 34 +/- 10 bpm, P < .01), resting mean blood pressure was significantly decreased 24 hours after the lesions (delta = -19 +/- 5 mm Hg, P < 01). No significant changes in cardiac baroreflex were observed in sham-lesion rats (n = 12). Histological examination showed circumscribed bilateral damage of dorsolateral periaqueductal gray matter. Dorsolateral periaqueductal gray matter is an area of the brain putatively related to fear and anxiety. It also projects onto premotor sympathetic neurons in the medulla. Although electrolytic lesions damage neurons as well as fibers of passage, these data suggest that dorsolateral periaqueductal gray matter has a far greater influence on resting cardiovascular control in spontaneously hypertensive rats than was previously suspected.

Animals↗

PubMed1994

Neurones in the medullary raphe nuclei attenuate the cardiovascular responses evoked from the dorsolateral periaqueductal grey matter.

In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation in the dorsolateral part of the periaqueductal grey matter (PAG; 10 s trains of 1 ms pulses at 80 Hz, 40-80 microA) evoked a pressor response accompanied by tachycardia. Both components of the response were attenuated following microinjection of 200 nl 0.1 M D,L-homocysteic acid into the caudal pole of the nucleus raphe magnus (NRM; n = 12) and into the nucleus raphe obscurus (NRO; n = 22) to selectively activate neuronal perikarya. Microinjection of 200 nl 165 mM NaCl into the same region (n = 15) had no effect. The attenuation of the midbrain-evoked cardiovascular responses lasted for 10-20 min and was independent of changes in resting blood pressure and heart rate. The maximum reduction in the pressor component of the midbrain-evoked responses was similar following stimulation in NRM (-35.4%) and NRO (-36.7%). However, the reduction in the midbrain-evoked tachycardia was greater following stimulation in NRM (-62.8%) compared to NRO (-27.2%). These results indicate that neurones in NRM and NRO may be involved in modulating the level of excitability of the midbrain defence area in the PAG and/or its efferent pathway.

Animals↗

PubMed1993

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.

Adaptation, Psychological↗

PubMed1993

Cardiac baroreflex dynamics during the defence reaction in freely moving rats.

To determine the extent of baroreceptor reflex involvement in the cardiovascular changes observed during electrically induced defence reaction, the mean arterial blood pressure (MBP) and heart rate (HR) of conscious intact or sinoaortic baroreceptor denervated (SAD) rats were continuously recorded from indwelling cannulae during a 1-min period of electrical stimulation of the mesencephalic tectum. Electrical stimulation produced stimulus intensity-dependent behaviours including freezing at lower intensities and flight at higher intensities. The cardiovascular responses in intact rats were dependent on both the intensity and duration of the stimulus. A linear increase in MBP was observed with increasing stimulus intensities. However, while a slight bradycardia was observed during the freezing behaviour, a marked tachycardia occurred during flight. Simultaneous increases of MBP and HR were seen throughout the first 15 s of the flight response, after which the HR rapidly fell to baseline levels, whereas the MBP remained at a hypertensive plateau until the end of the stimulus. The baroreflex HR curve showed a parallel shift to the left during the first half of the freezing period, being fully reset 40 s after that. So, while the baroreflex gain remained unchanged, the reflex set point was lowered during the freezing stage of the defence reaction. The experiments with SAD rats corroborated the above data. The baroreceptor denervation reversed the freezing bradycardia to tachycardia. Moreover, the denervation potentiated the flight tachycardia and prevented its later reset. MBP responses of baroreceptor denervated rats did not differ from the sham-operated group. The sustained hypertension, thus, appears to be mediated by mechanisms other than the mere baroreceptor reflex deactivation. (ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

PubMed1990

Logistic analysis of the defense reaction induced by electrical stimulation of the rat mesencephalic tectum.

Subliminal and threshold functions of behavioral output to electrical stimulation of the rat mesencephalic tectum were fitted using the logistic model. The results suggest the existence of isotopic albeit anisotropic freezing and flight mechanisms in the dorsal periaqueductal gray and deep layers of the superior colliculus. Moreover, the marked parallelism of immobility and running threshold functions indicates the probable coupling of these mechanisms through a kind of negative feedback. Finally, the good fitting to the model suggests that the behavioral output to electrical stimulation of these areas follows a logistic function of the logarithm of the stimulus intensity.

Aggression↗

PubMed1989

Cardiovascular change in response to prolonged defense area stimulation in freely moving rats.

The mean blood pressure and heart rate of freely moving rats were directly recorded over a 1-min period of electrical stimulation of the periaqueductal gray with intensities that induced freezing behavior, intense flight or no behavioral changes. Blood pressure and heart rate increased only when flight was induced and only during the first 15 s of stimulation. These cardiovascular changes suggest that homeostatic mechanisms act during the defense reaction and are markedly inhibited only at the beginning of the stimuli that induce the flight response, this inhibition quickly undergoing attenuation. These data do not suggest that activation of defense area, per se, contributes to the development of primary hypertension.

Animals↗

PubMed1983

GABA modulation of the defense reaction induced by brain electrical stimulation.

Earlier behavioral results led to the suggestion that GABA exerts a tonic inhibitory influence in the dorsal periaqueductal gray (DPAG) matter of the rat integrating defensive behavior. In the present experiments, the role of GABAergic mechanisms in the modulation of the autonomic component of the defense reaction was studied. Thus, the effects of intravenous (IV) injections of chlordiazepoxide as well as of intracerebral (IC) injections of midazolam in the dorsal midbrain, on the blood pressure (BP), heart rate (HR) and respiratory increases induced by electrical stimulation of the DPAG were measured in rats anesthetized with urethane. Chlordiazepoxide (10 mg/kg, IV) as well as midazolam (40 and 160 nmol, IC) attenuated the centrally-induced hypertension, without affecting basal BP. The tachycardia induced by aversive brain stimulation was similarly decreased by the benzodiazepines. In addition, the HR baseline was significantly raised by chlordiazepoxide and by the highest dose of midazolam. The tachypnea induced by brain electrical stimulation was also reduced by both benzodiazepines. Basal respiratory rate was slightly, but significantly decreased by chlordiazepoxide as well as by the two doses of midazolam used and to a lesser extent by the vehicle alone. Chlordiazepoxide attenuated the increase in respiratory depth caused by brain stimulation, while basal respiratory amplitude was not affected. The effects of midazolam on this parameter were unclear. Microinjection of bicuculline (5 and 10 nmol) or picrotoxin (0.3 and 1 nmol) into the DPAG increased the BP, HR and respiration, like the electrical stimulation. The latency and duration of bucuculline effects were shorter than those of picrotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗