Dorsal Periaqueductal Gray Matter Research Articles

NPY Y1 receptors in the dorsal periaqueductal gray matter regulate anxiety in the social interaction test.

We have reported previously that the NPY Y1 receptor antagonist BIBP3226 applied into the dorsal periaqueductal gray matter (DPAG) has an anxiogenic-like effect in the elevated plus-maze test in rats. In the present study the effects of neuropeptide Y (NPY) Y1 receptor antagonists BIBP3226 (500 pmol) and 1229U91 (formerly also GR231118, GW1229 and EXBP68, 100 and 500 pmol) administered into the DPAG were investigated in the social interaction test in rats. BIBP3226 and 1229U91 (both 500 pmol) significantly decreased the time spent in active social interaction. These results provide additional evidence that NPY-ergic neurotransmission in the DPAG may be involved in the modulation of anxiety-related behaviour and suggest that endogenous NPY, released under stressful conditions in the DPAG, relieves anxiety via the NPY Y1 receptors. This is the first report demonstrating the effect of NPY receptor active agent on social behaviour.

Kainate Microinjection into the Dorsal Raphe Nucleus Induces 5-HT Release in the Amygdala and Periaqueductal Gray

Earlier results obtained in one of our laboratories showed that microinjection into the dorsal raphe nucleus (DRN) of the excitatory amino acid kainic acid, the benzodiazepine (BZD) inverse agonist FG 7142, and the 5-HT 1A receptor agonist 8-OH-DPAT changed the behavior of rats in the elevated T-maze, an animal model of anxiety. The present study investigates biochemical correlates of these results in awake rats by measuring 5-HT release with in vivo microdialysis in two brain structures innervated by the DRN—the amygdala (Am) and the dorsal periaqueductal gray matter (DPAG)—that have been implicated in anxiety. Microinjection of kainic acid (60 pmol) into the DRN significantly increased 5-HT release in both the Am and the DPAG. In the DPAG, the increase was 14-fold higher with respect to the baseline and occurred only at the first sample, which was collected 30 min after the injection. In the Am, the increase was less pronounced (nearly fourfold) but persistent, lasting until the fourth sample, which was collected 120 min from the injection. FG 7142 (40 pmol) and 8-OH-DPAT (8 nmol) were ineffective. Because only intra-DRN kainate both increased inhibitory avoidance and decreased one-way escape in the elevated T-maze, the present behavioral results support the suggestion that 5-HT facilitates conditioned fear in the Am and inhibits unconditioned fear in the DPAG.

Effects of 5-HT 2 receptors blockade on fear-induced analgesia elicited by electrical stimulation of the deep layers of the superior colliculus and dorsal periaqueductal gray

The deep layers of the superior colliculus (DLSC) and the dorsal periaqueductal gray matter (DPAG) have been implicated in the control of defensive-like behaviors. Electrical and chemical stimulation of these structures elicits fear and escape behaviour, expressed by immobility (freezing) and wild running, followed by jumps and rapid rotations. There is evidence that the neural substrates responsible for defensive behavior in this level of the midbrain tectum (MT) may also be responsible for fear-induced analgesia. This study was aimed at examining the characteristics of the analgesia that follows the defense-oriented reactions induced by electrical midbrain tectum stimulation at freezing and escape thresholds. The animals were submitted to the tail-flick test, following the induction of the defensive behavioral responses. The obtained results show that the antinociception that follows the freezing and escape behaviours were not antagonized by MT microinjections of the opioid antagonist naltrexone. These results emphasize previous data showing the non-opioid nature of this analgesia. On the other hand, the fear-induced analgesia was inhibited by microinjections of the serotonergic blockers, methysergide and ketanserin in the MT. Since methysergide is a non-specific antagonist of 5-HT receptors and ketanserin acts with a high degree of specificity at 5-HT 2 receptors the present results suggest that activation of 5-HT 2 receptors may be implicated in the antinociception induced by midbrain tectum stimulation.

Central C-Fos Expression Following 20kHz/Ultrasound Induced Defence Behaviour in the Rat

Exposure of rats to aversive stimuli produces specific defence behaviour including the emission of 20–27kHz ultrasonic calls. Recent studies in this laboratory have shown that rats exposed to a 20kHz ultrasound tone display flight behaviour similar to that seen naturally, or following stimulation of brain regions associated with anxiety and defence. The present study examines the effect of ultrasound exposure on the central expression of the immediate early gene c-fos in the rat, in order to examine the brain structures activated by such behaviour.Ultrasound presentation produced rapid locomotor activity characteristic of defence behaviour, including brisk running and jumping behaviour. Animals showed dense c-fos like immunoreactivity in the dorsal periaqueductal grey matter, basolateral, medial, central amygdala, paraventricular thalamic nuclei and the dorsomedial nuclei of the hypothalamus, which was significantly greater than in either home-cage or arena control rats.These results suggest that exposure to artificially generated ultrasound can induce defence behaviour which is associated with activity in brain regions important in mediating aversion. This technique offers the potential of generating unconditioned aversive behaviour in rats in a non invasive way.

Behavioral effects of CCK B receptor ligands in a validated simulation of panic anxiety in rats

Animals or human subjects receiving brain stimulation in the dorsal periaqueductal gray matter (dPAG) show sudden fear-suggestive behavioral reactions and physical signs of autonomic activation which are reminiscent of the symptom profile characterizing a panic attack. An experimental situation in rats measuring dPAG stimulation self-interruption thresholds has been validated as realistically simulating several aspects of panic anxiety with objective signs of symptomatic and predictive validity using established antipanic and panicogenic agents; it was utilized here to evaluate the effects of various cholecystokinin B receptor ligands. A dose-dependent increase in self-interruption thresholds (antipanic-like effect) was recorded following injection of L-365,260 (3.2, 10 and 32 mg/kg i.p.), a CCK B receptor antagonist with good brain penetration, whereas no significant changes in thresholds were recorded following CI-988 (3.2, 10 and 32 mg/kg i.p.), a dipeptoid CCK B receptor antagonist with poor brain penetration. Latencies for self-interruption were not modified, suggesting that motor functions remained intact. No significant changes in self-interruption thresholds were recorded following peripheral administration of the CCK B receptor agonists CCK 4 (0.03 to 0.32 mg/kg i.v.; 0.01 to 3.2 mg/kg i.p.) or the metabolically stabilized analog Boc-CCK 4 (0.1 to 10 mg/kg i.p.). Systemic administration of the panicogenic compounds caffeine and yohimbine enhance acute anxiety in this model. These data indicate that, in the dPAG simulation of panic anxiety, central CCK B receptor blockade by L-365,260 induces antiaversive effects analogous to those observed following benzodiazepine receptor activation by clonazepam or alprazolam. Potency and efficacy of L-365,260 were lower than those of clonazepam or alprazolam, suggesting modest, but nonetheless authentic, antiaversive properties for this CCK B receptor antagonist. Lack of effects observed following peripheral administration of the agonists CCK 4 and Boc-CCK 4 or of the dipeptoid antagonist CI-988 is likely to reflect restricted brain penetration of those compounds in rats; it furthermore excludes a contribution of peripheral gastrin and CCK A receptors to the antipanic-like properties of selective CCK B receptor antagonists such as L-365,260.

Effects of microinjections of the neuropeptide substance P in the dorsal periaqueductal gray on the behaviour of rats in the plus-maze test

Currently, the participation of neuropeptides in the generation of aversive states in the dorsal periaqueductal gray matter (DPAG) is poorly understood. The elevated plus maze (EPM) is widely used for studying the neurobiological mechanisms of anxiety in the laboratory. One difficulty with this test has been to evaluate the involvement of GABA mechanisms in the DPAG substrates of aversion, because microinjections of GABA receptor blockers in this region cause an intense behavioral activation. In this study, we examined in the EPM the effects of semicarbazide, a drug that acts indirectly on GABA neurotransmission through inhibition of the glutamic acid decarboxylase, and substance P (SP) following microinjections into the dorsal periaqueductal gray. Semicarbazide caused a clear decrease in the number of entries and time spent in the open arms. These results confirm previous data showing that GABA has a modulatory role in the DPAG, probably through reduction of tonic inhibitory mechanisms on neural substrates of aversion. A similar pattern of behavioral responses was observed with SP. However, these effects were more pronounced with intermediate doses of SP (25 ng), confirming the characteristic bell-shaped dose-effect function of this neuropeptide. The proaversive effects observed with DPAG microinjections of SP in the present study gain further relevance when combined with previous reports that have shown unconditioned and conditioned aversive effects following DPAG microinjections of SP in other animal models of aversion.

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.

Dorsal periaqueductal gray-induced aversion as a simulation of panic anxiety: Elements of face and predictive validity

Neurosurgical stimulation of the dorsal periaqueductal gray (dPAG) matter in man induces acute signs of autonomic arousal and feelings of subjective anxiety; those signs have phenomenological similarity with the symptom profile characterizing a panic attack. Animals undergoing dPAG stimulation show comparable physical signs of autonomic activation and sudden fear-suggestive behavioral reactions that can be shaped into operant self-interruption behavior. Drugs known to acutely reduce (alprazolam, clonazepam) or precipitate (yohimbine, caffeine) panic attacks in patients were found to acutely and dose-dependently reduce or enhance, respectively, aversion induced by dPAG stimulation in rats. When considered as an animal model of panic anxiety, the dPAG model simultaneously meets criteria of face validity (symptomatic homology) and predictive validity (pharmacological homology under short-term treatment); aspects of its construct validity (theoretical rationale supporting the model) are discussed. It is suggested that dPAG stimulation-induced aversion may represent a model of some aspects of panic disorders.

Anxiogenic-like effect of glycine and d-serine microinjected into dorsal periaqueductal gray matter of rats

The glutamatergic system of the dorsal periaqueductal gray matter (DPAG) has been implicated in anxiety. This study shows that microinjections of glycine (GLY) or d-serine ( d-SER), into the DPAG of rats, dose-dependently reduced the number of entries and the time spent on open arms of an elevated plus-maze (EPM), an established animal model for measuring anxiety-related behavior. This anxiogenic-like effect was greatest following DPAG application of either 80 nmol GLY or 160 and 320 nmol d-SER. Microinjections of these same amino acid doses outside the DPAG, or of l-serine (320 nmol) inside the DPAG, produced neither of these pro-anxiety effects. The current results suggest that, in vivo, the GLY modulatory site of N-methyl- d-aspartate receptors is not fully saturated, and further substantiate a role for the DPAG excitatory amino acid system in anxiety.

GABAergic nigro-collicular pathways modulate the defensive behaviour elicited by midbrain tectum stimulation.

Midbrain tectum (MT) structures such as the dorsal periaqueductal gray matter and deep layers of superior colliculus are well-known for the organization and generation of defensive behaviour. Electrical stimulation or microinjection of GABA antagonists into these structures produce aversive behaviour. In order to determine whether the nigrocollicular GABAergic fibers exert some control over this behaviour, rats bearing neurochemical lesions with kainic acid in the substantia nigra, pars reticulata (SNpr) and compacta (SNpc), were submitted to MT microinjections of bicuculline or electrical stimulation at aversive thresholds. The same procedure was carried out after enhancement or inhibition of GABAergic transmission in SNpr through microinjections of muscimol or bicuculline, respectively. Animals with SNpr neurochemical lesion exhibited a significant decrease in the aversive thresholds and an increase in the responsiveness to bicuculline microinjections. An opposite effect was observed following microinjections of bicuculline into the SNpr. The enhancement of the GABAergic transmission into the SNpr following microinjection of muscimol mimicked the effects produced by the lesion with kainic acid. These results suggest an inhibitory control of GABAergic fibers from the substantia nigra, pars reticulata, on aversive behaviour induced by midbrain stimulation.

The periaqueductal gray-rostral medulla connection in the defence reaction: efferent pathways and descending control mechanisms.

Neuronal systems controlling cardiovascular components of emotional responses must have the capacity to generate different patterns of response and must also be able to modify those patterns in response to changes in environmental circumstances. Using the cardiovascular "defence" response as a model, evidence is presented to show that sympathetic premotor neurons of the rostral ventrolateral medulla (RVLM) possess such properties. Neurones in the RVLM act as relays in the descending efferent pathway to the sympathetic outflows from the dorsal periaqueductal gray matter (dPAG) which integrates the characteristic "defensive" pattern of cardiovascular response that accompanies activation of the midbrain aversive system. Activity in this pathway can be modulated, at the level of the RVLM, by a descending pathway which originates in the ventrolateral PAG. It is suggested that both the dorsolateral and the ventrolateral control systems in the PAG become activated during periods of physical or emotional stress, particularly those which involve sustained motor activity. Activity in the dorsal system initiates cardiovascular components of aversive/defensive behaviour whilst the ventrolateral system plays an important role in initiating the recuperative phase of behaviour characterised by sympathoinhibition, muscular relaxation and immobility which follows a stressful encounter.

Role of benzodiazepine receptors located in the dorsal periaqueductal grey of rats in anxiety

Studies with electrical brain stimulation suggest that the dorsal periaqueductal grey matter (DPAG) is related to anxiety and to the anti-aversive effects of benzodiazepines (BZD) compounds. However, direct stimulation of the brain may prevent conclusions about the role of specific regions in the control of normal behaviour. In the present study we employed the elevated plus-maze, an ethologically based model of anxiety, to investigate the role of BZD receptors located in the DPAG in anxiety and in the anxiolytic effect of systemically injected BZD. The results showed that midazolam (20-80 nmol), a BZD agonist, dose-dependently increased the percentage of entries and time spent in open arms when microinjected into the DPAG. The effect of midazolam (80 nmol) was antagonized by flumazenil (80 nmol), a BZD antagonist, microinjected into the DPAG 10 min before the agonist. FG 7142 (20-80 nmol), a BZD partial inverse agonist, decreased time spent in open arms at the dose of 40 nmol and the number of open arms entries at all doses when microinjected into the DPAG. The microinjection of flumazenil (80 nmol) into the DPAG failed to antagonize the anxiolytic effect of systemically injected diazepam (2.5 mg/kg). These results strengthen the idea of an involvement of BZD receptors located in the DPAG with anxiety. They also suggest that the DPAG is not the only structure responsible for the anxiolytic effects of systemically injected BZD.

Attenuation of chemically induced defence response by 5-HT1 receptor agonists administered into the periaqueductal gray.

The ability of 5-HT1 receptor agonists to modulate a chemically induced defence response has been studied in Lister hooded rats. Microinjections of the excitatory amino acid D,L-homocysteic acid (DLH) in both rostral and caudal dorsal periaqueductal gray matter (PAG) caused explosive motor behaviour characteristic of defence. This behaviour was quantified in terms of response duration, arena revolutions and number of defensive jumps. Direct administration into the PAG of either 5-carboxamidotryptamine (5-CT) or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) produced behaviours (decreased exploratory rearing, dose related onset of flat body posture) indicative of 5-HT1A receptor activation. Pretreatment with either 5-CT or 8-OHDPAT directly in the PAG caused a significant attenuation, and in some cases a complete abolition, of the DLH evoked response. These agonists share high affinity in vitro for the 5-HT1A receptor. Thus the results suggest that in vivo activation of 5-HT1A receptors mediates an antiaversive response with respect to defensive behaviour elicited by specific chemical stimulation of the dorsal PAG.

Dorsal mesencephalic projections to pons, medulla, and spinal cord in the cat: limbic and non-limbic components.

The vertebrate dorsal mesencephalon consists of the superior colliculus, the dorsal portion of the periaqueductal gray, and the mesencephalic trigeminal neurons in between. These structures, via their descending pathways, take part in various behavioral responses to environmental stimuli. This study was undertaken to compare the origins and trajectories of these pathways in the cat. Injections of horseradish peroxidase into the cervical spinal cord and upper medullary medial tegmentum retrogradely labeled cells mainly in the contralateral intermediate and deep superior colliculus, and in the ipsilateral dorsal and lateral periaqueductal gray and adjacent tegmentum. Only injections in the medullary lateral tegmental field labeled mesencephalic trigeminal neurons ipsilaterally. Autoradiographic tracing results, based on injections across the dorsal mesencephalon, revealed three efferent fiberstreams. A massive first fiberstream (limbic pathway), consisting of thin fibers, descended ipsilaterally from the dorsal and lateral periaqueductal gray and adjacent superior colliculus through the mesencephalic and pontine lateral tegmentum, terminating in these areas as well as in the ventral third of the caudal pontine and medullary medial tegmentum. A few fibers from the dorsal periaqueductal gray matter (PAG) were distributed bilaterally to the dorsal vagal, solitary, and retroambiguus nuclei. The second fiberstream (the predorsal bundle) descended contralaterally from the superior colliculus (SC) and consisted of both thick and thin labeled fibers. The thin fibers terminated bilaterally in the dorsomedial nucleus reticularis tegmenti pontis and the medial half of the caudal medial accessory inferior olive. The thick fibers targeted the contralateral dorsal two thirds of the caudal pontine and medullary medial tegmental fields, and the facial, abducens, lateral reticular, subtrigeminal, and prepositus hypoglossi nuclei. A few fibers recrossed the midline to terminate in the ipsilateral medial tegmentum. Caudal to the obex, fibers terminated laterally in the tegmentum and upper cervical intermediate zone. From the lateral SC, fibers terminated bilaterally in the lateral tegmental fields of the pons and medulla and lateral facial subnuclei. The third fiberstream (mesencephalic trigeminal or Probst tract) terminated in the supratrigeminal and motor trigeminal nuclei, and laterally in the tegmentum and upper cervical intermediate zone. In summary, neurons in the PAG and in the deep layers of the SC give rise to a massive ipsilateral descending pathway, in which a medial-to-lateral organization exists. A similar topographical pattern occurs in the crossed SC projections. The possibility that these completely different descending systems cooperate in producing specific defensive behaviors is discussed.

Inhibitory modulation of the cardiovascular defence response by the ventrolateral periaqueductal grey matter in rats.

In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation in the dorsal periaqueductal grey matter (PAG) evoked a pressor response with tachycardia, vasodilatation in the hindlimb and hyperpnoea: a pattern of response known as the defence reaction. Microinjection of the synaptic excitant, D,L-homocysteic acid (DLH), but not saline, into the ventrolateral PAG at the level of the decussation of the superior cerebellar peduncle (approximately 7.3-8.3 mm caudal to bregma) produced a reduction in the size of the cardiovascular components of the defence reaction evoked by electrical stimulation in the dorsal PAG. Injections of DLH made outside this region had no effect on the defence response. Injection of DLH into the "defence inhibition area" had no effect on the pressor response evoked distally in the efferent pathway for the defence reaction, by electrical stimulation in the rostral ventrolateral medulla (RVLM). Activation of neurones in a restricted portion of the caudal ventrolateral PAG appears to modulate activity in the descending pathway for the defence response evoked from the dorsal PAG. It is argued that the inhibitory interaction probably occurs at the level of synapses in the RVLM.

Convergent inputs to neurones in the nucleus paragigantocellularis lateralis in the cat

Extracellular recordings were made in the nucleus paragigantocellularis (PGL) of the cat in response to stimulation of the hypothalamic perifornical defence area (HPDA), dorsal periaqueductal grey matter (PAG), nucleus raphe obscurus (Rob), deep peroneal nerve (DPN), and superficial peroneal nerve (SPN). Stimulation of the HPDA, dorsal PAG and SPN evoked excitatory responses whilst the prevalent response to stimulation of Rob was inhibition. However, most of the defence-reaction-related neurones showed little response to stimulation of DPN. Of 53 cells tested 48 (91%) received convergent inputs from two or more sites of stimulation. These findings are discussed in relation to the integrative function of PGL in cardiovascular control.

Changes in blood pressure during isometric contractions to fatigue in the cat after brain stem lesions: effects of clonidine

The aim was to determine whether areas in the periaqueductal grey matter, medial dorsal raphe, or ventrolateral medulla might be involved with the integration of blood pressure and heart rate during isometric exercise. Cats were anaesthetised with alpha chloralose (75 mg.kg-1) and catheters inserted into the right jugular vein and carotid artery. Isometric contractions were generated using a microprocessor controlled stimulator and sleeve electrode around the tibial nerve. Bilateral lesions were made in the dorsal periaqueductal grey matter (P1.0, LR2.0, HD + 1.5 mm) or two sites in the ventrolateral medulla (P12.0, RL 2.0, HD -10 mm; or P12.0, RL 2.0, HD -8.5 mm). Lesions were also made in the medial dorsal raphé nuclei (P1.0, RL 0.0, HD +1.5 mm). Clonidine was injected into the cerebral aqueduct to determine whether it would exert an antipressor effect during muscle contraction after the lesions were made. Only one site of lesion was made in a group of animals. Bilateral injections of clonidine (250 ng in 0.5 microliter) were made into the intact ventrolateral medulla (P11.5, RL 4.0, HD -8.5 mm) to explore its role further. Fatiguing contractions were performed before and after the lesions were made, or clonidine was injected, and changes in arterial blood pressure and heart rate were measured. Verification of the lesion sites or the microinjection sites, and the extent of the lesion or spread of the clonidine, was made from histological examination of brain tissue after each experiment. Adult cats of either sex, n = 20, weight 2.4 (SD 0.4) kg, were used. Fatiguing isometric contractions in control conditions caused mean arterial pressure to increase by 45-50 mm Hg and heart rates by 20-25 beats.min-1. Bilateral lesions in the dorsal periaqueductal grey matter did not alter resting mean arterial pressure but attenuated the pressor response during contractions. Injections of clonidine into the cerebral aqueduct had no further antipressor effects after the lesions. Lesions of the medial dorsal raphé nuclei or injections of clonidine into the intact medial dorsal raphé nuclei did not affect the pressor response to fatiguing isometric contractions. Injections of clonidine into the intact ventrolateral medulla eliminated the pressor response to isometric contractions. Bilateral lesions of the ventrolateral medulla near the rostral lateral border of the inferior olivary tract nuclei (P12.0, LR 2.0, HD -10 mm) also attenuated the muscle pressor response, while subsequent injections of clonidine into the cerebral aqueduct depressed the changes in blood pressure further. Ergoreceptor information may be processed through the periaqueductal grey matter through the ventrolateral medulla to control arterial blood pressure during isometric exercise to fatigue.

Convergent afferent inputs to neurones in nucleus paragigantocellularis lateralis in the cat

Neuronal activity was recorded in nucleus paragigantocellularis lateralis (PGL) of the cat in response to stimulation of the dorsal periaqueductal grey matter (dPAG), parabrachial nucleus (PBN) nucleus raphe magnus (NRM), and nucleus tractus solitarii (NTS). Stimulation in dPAG or PBN evoked excitatory responses whilst the prevalent response to stimulation in NRM or NTS was inhibition of neuronal activity. 45/55 (82%) of cells tested received convergent inputs from 2 or more sites of stimulation. These findings are discussed in relation to the role of PGL in cardiovascular control and descending control of noxious input.

Flight behavior induced by microinjection of GABA antagonists into periventricular structures in detelencephalated rats.

Behavioral effects of unilateral microinjections into periventricular structures of bicuculline, a classic GABA-A antagonist, and semicarbazide, a glutamic acid decarboxylase blocker, were studied in detelencephalated rats. These drugs produced a behavioral activation together with jumps. However, the characteristics of this behavioral activation differed as the injections were made in dorsal periaqueductal gray matter or medial hypothalamus. These data show close similarities to those observed with intact animals suggesting that GABA-A receptors are involved in the neural control of expression of flight behavior and functions in an intact manner and possibly independent of influences from forebrain structures. At variance with intact animals, these drugs produced contralateral turning behavior when locally injected into MH, pointing to some kind of inhibitory control exerted by telencephalic structures on the expression of circling behavior from diencephalic regions.

Defense reaction induced by microinjections of bicuculline into the inferior colliculus

Behavioral and autonomic effects of microinjections of bicuculline—a GABA receptor antagonist—into ventral aspects of the inferior colliculus (IC) produced a behavioral activation together with jumps. This activation was similar to escape behavior that has been induced from periventricular structures although it was neither as explosive as that observed from the dorsal periaqueductal gray matter (DPAG) nor as coordinated as that obtained from the medial hypothalamus (MH). In anesthetized rats, microinjection of bicuculline into the IC produced a clear rise in mean arterial blood pressure and in heart rate. These effects reached a maximum after 10 min and subsided within 20 min after injection. GABA receptor blockade in the IC of detelencephalated rats also resulted in escape behavior qualitatively similar to that observed in intact animals. These results suggest that in addition to the central gray and medial hypothalamus, GABA also exerts a tonic inhibitory action on neurons of the IC implicated in the generation or elaboration of aversive responses.