Biomedical subjects

M B Shaikh

Publications and source records attributed to M B Shaikh.

At least 19 recordsLinked to original sources

PubMed1993

Evidence that substance P is utilized in medial amygdaloid facilitation of defensive rage behavior in the cat.

The present study was designed to test the hypothesis that a major excitatory mechanism for the expression of feline defensive rage behavior involves the medial nucleus of the amygdala which utilizes substance P as a neurotransmitter in a direct output pathway that supplies the medial hypothalamus. In phase I of the experiment, stimulating electrodes were implanted into the medial amygdala and cannula electrodes were implanted into the medial and lateral hypothalamus from which defensive rage and predatory attack behavior could be elicited by electrical stimulation, respectively. Response latencies for defensive rage were significantly lowered after dual stimulation of the medial amygdala and medial hypothalamus relative to single stimulation of the medial hypothalamus alone. In phase II, dose- and time-dependent decreases in medial amygdaloid-induced facilitation of defensive rage were observed after the i.p. administration of the NK1 antagonist, CP-96,345 (0.05, 2 and 4 mg/kg). In phase III of the study, the effects of microinjections of CP-96,345 placed directly into defensive rage sites within the medial hypothalamus (0.05, 0.5 and 2.5 nmol) upon medial amygdaloid modulation of this response were assessed. Again, intracerebral administration of this antagonist blocked the facilitatory effects of medial amygdaloid-induced facilitation of defensive rage in a manner parallel to that observed with peripheral administration of the NK1 antagonist. The results suggest that the medial amygdala facilitates defensive rage by acting through a substance P mechanism at the level of the medial hypothalamus. Other experiments revealed that peripheral administration of the NK1 antagonist: (1) had little upon the latency or threshold for elicitation of defensive rage, suggesting that the medial amygdaloid-substance P facilitatory mechanism acts in a phasic rather than tonic manner; and (2) also blocks the suppressive effects of medial amygdaloid stimulation upon predatory attack behavior elicited from the lateral hypothalamus. The latter finding suggest that similar neurochemical mechanisms regulate medial amygdaloid modulation of both forms of hypothalamically elicited aggression. The final aspect of this study utilized the combination of retrograde-tracing of amygdaloid neurons into the medial hypothalamus after microinjections of Fluoro-Gold into defensive rage sites, and the immunocytochemical analysis of substance P neurons within the amygdala. The data indicated that large numbers of retrogradely and immunocytochemically positive labeled cells were identified in the medial nucleus, including many that were double-labeled.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗

PubMed1992

Role of NMDA receptors in hypothalamic facilitation of feline defensive rage elicited from the midbrain periaqueductal gray.

The present study tested the hypothesis that the pathway from the medial hypothalamus to the midbrain periaqueductal gray (PAG) subserving defensive rage behavior in the cat facilitates the occurrence of this response when elicited from the PAG by utilizing excitatory amino acids as a neurotransmitter or neuromodulator. Cannula electrodes were implanted into the PAG for the elicitation of defensive rage behavior as well as for microinjections of excitatory amino acid antagonists and N-methyl-D-aspartic acid (NMDA). Monopolar stimulating electrodes were also implanted into the medial hypothalamus from which this response could also be elicited and, when stimulated at subthreshold levels for elicitation of behavior, could also facilitate the occurrence of PAG elicited defensive rage. Initially, dual stimulation of the PAG and medial hypothalamus facilitated the occurrence of defensive rage elicited from the PAG. Then, the identical dual stimulation paradigm was repeated with the same current parameters following the infusion of various antagonists for different receptors into the PAG defensive rage sites. The results indicate that infusion of either kynurenic acid [(0.1-2.0 nmol), a non-selective excitatory amino acid receptor antagonist] or D-2-amino-7-phosphonoheptanoic acid (AP7) [(0.1-2.0 nmol), a specific NMDA receptor antagonist], produced a dose and time dependent blockade of the facilitatory effects of medial hypothalamic stimulation. In contrast, microinjections of relatively larger doses of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) [(4 nmol), a non-NMDA receptor (quisqualate and kainate) antagonist] or atropine [(4.4 nmol), a muscarinic receptor antagonist] had little effect upon medial hypothalamically elicited facilitation of the PAG response. In a second experiment, NMDA [0.1-1.0 nmol] was microinjected directly into PAG defensive rage sites in the absence of medial hypothalamic stimulation. In these animals, drug infusion mimicked the effects of dual stimulation by producing a dose and time dependent decrease in response latencies. A third experiment was designed to further test the hypothesis by neuroanatomical methods. Here, the retrograde label, Fluoro-Gold, was microinjected into defensive rage sites within the PAG and following a survival time of 5-6 days, the animals were sacrificed. The brains were then processed for immunocytochemical analysis of cells that immunoreact positively for aspartate and glutamate. The results indicated the presence of many retrogradely labelled and immunocytochemically positive cells within the rostro-caudal extent of the medial hypothalamus as well as others that were double labelled.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1991

An enkephalinergic mechanism involved in amygdaloid suppression of affective defence behavior elicited from the midbrain periaqueductal gray in the cat.

A series of recent studies in our laboratory have provided evidence that opioid peptides powerfully suppress feline affective defense behavior at the level of the midbrain periaqueductal gray (PAG). In the present study, we tested the hypothesis that the central (CE) nucleus of the amygdala constitutes a significant inhibitory input to the PAG which utilizes enkephalins as its neurotransmitter or neuromodulator. Cannula-electrodes were implanted into the PAG for the elicitation of affective defense behavior as well as for infusion of opioid antagonists. Monopolar stimulating electrodes were also implanted into the central, lateral and medial amygdaloid nuclei from which suppression or facilitation of affective defense behavior could be obtained. Initially, 4 trials of concurrent, subseizure stimulation of the CE or lateral amygdala at very low (100 microA, 60 Hz) currents and PAG resulted in an immediate suppression of this response which displayed a time dependent decline after 30 min. In the next stage of the experiment, naloxone (2.7, 18.9 and 27.5 nM) was microinjected through the cannula-electrode into the PAG affective defense site and the experimental procedures noted above were repeated. Naloxone treatment (at 27.5 and 18.9 nM) blocked the suppressive effects of CE and lateral amygdaloid stimulation in a dose and time dependent manner. Further analysis revealed that this effect is likely mediated via the mu receptor since the suppressive effects of amygdaloid stimulation were blocked by the selective mu antagonist, beta-Funaltrexamine (0.05 and 0.2 nM) but not by the selective delta-antagonist, ICI 174,864 (0.7 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Affect↗

PubMed1991

Affective defense behavior elicited from the feline midbrain periqueductal gray is regulated by mu and delta opioid receptors.

The present study sought to identify specific opioid receptor subtypes involved in the modulation of affective defense behavior (AD) at the level of the midbrain periaqueductal gray (PAG). Cannula electrodes were utilized for eliciting AD from the PAG as well as for microinjecting mu, delta and kappa agonists and antagonists into these sites. Following microinjections of morphiceptin, D-Pen2,D-Pen5 enkephalin (DPDPE), or U-488H into sites from which AD was elicited, threshold values were determined. The results indicated that morphiceptin and DPDPE significantly suppressed AD in a dose- and time-dependent manner. Pretreatment with mu and delta opioid antagonists, B-FNA and ICI 174,864, completely blocked the suppressive effects of morphiceptin and DPDPE, respectively. Microinjections of morphiceptin and DPDPE failed to alter response thresholds for circling behavior also elicited from electrical stimulation of dorsal PAG. Administration of the selective kappa agonist, U-488H, or vehicle alone, did not alter the threshold for AD. The results of this study indicate that opioid peptides interact with mu and delta receptors within the midbrain PAG to powerfully suppress AD.

Affect↗

PubMed1991

Enkephalinergic involvement in periaqueductal gray control of hypothalamically elicited predatory attack in the cat.

The effects of central infusion of naloxone into the midbrain periaqueductal gray (PAG) upon predatory attack behavior in the cat were studied in 12 cats. Initially, quiet biting attack was elicited by electrical stimulation of sites within the lateral hypothalamus using monopolar electrodes. Then cannula-electrodes were implanted into sites within the PAG from which electrical stimulation facilitated or suppressed the attack response. Following identification of modulatory sites within the PAG, naloxone (1.0 micrograms/0.5 microliter) was microinjected into those sites and the effects upon hypothalamically elicited attack were assessed. At nine of twelve sites in the PAG where suppression was obtained, administration of naloxone served to block those effects. Similarly, at six of eight facilitatory sites within the PAG, naloxone also blocked the modulatory effects of PAG stimulation. However, vehicle (isotonic saline) alone did not alter the modulatory effects of PAG stimulation. Administration of DAME (250 ng/0.3 microliter) into PAG modulatory sites in four cats, two which facilitated and two that suppressed the attack response, reversed the effects of naloxone at these sites. These results demonstrate that opioid peptides within the PAG play a complex role in the expression of predatory attack behavior in the cat.

Aggression↗

PubMed1991

Dopaminergic regulation of quiet biting attack behavior in the cat.

The present study provides evidence for the involvement of dopamine in the regulation of quiet biting attack behavior. Utilizing monopolar electrodes, quiet biting attack was elicited by electrical stimulation of lateral hypothalamus in five cats. After stable baseline response latency values were established, the nonselective dopamine agonist, apomorphine, was administered peripherally (IP, 1.0, 1.4 and 1.8 mg/kg), and its effects upon the attack response were identified. Apomorphine significantly facilitated the occurrence of quiet biting attack in a dose- and time-dependent manner. Conversely, quiet biting attack behavior was also suppressed in a dose- and time-dependent manner by the selective D2 antagonist, spiperone (0.2, 0.4 and 0.8 mg/kg), but not by the selective D1 antagonist, SCH 23390 (0.8 mg/kg). Moreover, pretreatment with spiperone (0.2 mg/kg) completely blocked the facilitatory effects of 1.4 mg/kg of apomorphine, while SCH 23390 (0.8 mg/kg) pretreatment failed to alter apomorphine-induced facilitation of the attack response. In addition, neither apomorphine nor spiperone altered response latencies for hypothalamically elicited circling behavior. The results suggest that dopamine plays a significant role in the regulation of quiet biting attack behavior.

Aggression↗

PubMed1990

GABA-mediated regulation of feline aggression elicited from midbrain periaqueductal gray.

The midbrain periaqueductal gray (PAG) is now recognized as a critical structure for the initiation and regulation of aggressive behavior in the cat. The PAG is also known to be rich in gamma-aminobutyric acid (GABA) receptors. In the present study, we sought to examine the possible role of this putative neurotransmitter in the modulation of affective defense and quiet biting attack behavior elicited by electrical stimulation of the PAG. Cannula-electrodes were employed for electrical stimulation as well as for microinjections of a GABA agonist (muscimol: 3, 12 and 22 pmol/0.25 microliters) and GABA antagonist (bicuculline: 22 and 68 pmol/0.25 microliters). After establishing predrug response threshold values for affective defense and quiet biting attack, these drugs were microinjected into the PAG sites from which these responses were elicited. Microinjections of muscimol (12 and 22 pmol) significantly suppressed the affective defense response in a dose- and time-dependent manner. Pretreatment with bicuculline (68 pmol) blocked the suppressive effects of muscimol (12 pmol) upon affective defense behavior. In contrast, this dose of muscimol failed to alter the response threshold for quiet biting attack behavior. Microinjections of vehicle alone (0.25 microliter of saline, pH = 7.4) did not modify the thresholds for either of these responses. These results indicate that, at the level of the PAG, GABA-ergic mechanisms are selectively involved in the regulation of affective defense behavior in the cat.

Aggression↗

PubMed1988

Naloxone-induced modulation of feline aggression elicited from midbrain periaqueductal gray.

In the present study, peripheral administration of naloxone hydrochloride (IP) was employed to identify the role of endogenous opioid peptides in the regulation of two forms of aggressive behavior in the cat--affective defense and quiet biting attack behavior. These forms of aggressive behavior were elicited by electrical stimulation of dorsal and ventral aspects of the midbrain periaqueductal gray, respectively, utilizing monopolar electrodes. Following the establishment of stable baseline thresholds for affective defense and quiet biting attack behavior, naloxone (0.5, 1.0, 4.0 and 7.0 mg/kg) and saline (vehicle control) were administered peripherally (IP). The response thresholds were tested 5-30, 30-60, 60-90, 180-210 and 1440-1470 min following naloxone administration. These results indicated that a dose level of 7.0 mg/kg of naloxone had a profound facilitatory effect on affective defense behavior. Response threshold values returned to prenaloxone baseline levels at 1440-1470 min postinjection. Administration of lower doses of naloxone (1.0 and 4.0 mg/kg) also resulted in a significant facilitation of this response but of shorter durations. Neither the lowest dose of naloxone (0.5 mg/kg) nor saline (vehicle control) were effective in modifying the threshold for affective defense behavior. In contrast, when tested for its effects upon quiet biting attack, the maximum dose utilized in this study (7.0 mg/kg) tended to suppress this response although the overall effect was not significant. The selective dose-dependent facilitatory effects of naloxone upon affective defense behavior in the cat suggests that the opioid peptide system plays a significant (inhibitory) role in the regulation of this response.

Aggression↗

PubMed1988

Carbamazepine regulates feline aggression elicited from the midbrain periaqueductal gray.

Carbamazepine has been utilized both as an anticonvulsant and as a psychotropic drug for the treatment of complex partial seizures and various mood and other emotional disorders such as the episodic dyscontrol syndrome. In the present study, we sought to identify the role of carbamazepine in the regulation of two forms of aggressive behavior--affective defense and quiet biting attack behavior--elicited by electrical stimulation of the midbrain periaqueductal gray matter of the cat in the absence of convulsive activity. The experimental paradigm involved establishment of stable baseline thresholds for affective defense and quiet biting attack responses. Following establishment of a stable baseline, carbamazepine (2.5, 5, or 10 mg/kg) and propylene glycol (vehicle control) were administered peripherally (IP). The response thresholds were tested 5-30, 30-60, 60-90, 120-150, 1440-1470, and 2160-2190 minutes following drug administration. It was observed that carbamazepine administration at 5 and 10 mg/kg dose levels preferentially suppressed affective defense behavior but had no effect upon quiet biting attack, indicating that the selective effects of carbamazepine upon affective attack are not due to any possible sedative effects upon motor responses. The effects of carbamazepine upon affective defense were dose dependent and of long duration when administered at the highest dose level (10 mg/kg).

Aggression↗

PubMed1987

The pathways mediating affective defense and quiet biting attack behavior from the midbrain central gray of the cat: an autoradiographic study.

The purpose of this study was to describe the pathways which mediate feline affective defense and quiet biting attack behavior elicited from the midbrain central gray. In these experiments, methods of [3H]leucine and 2-deoxy-[14C]glucose (2-DG) radioautography were utilized in concert with the technique of electrical and chemical brain stimulation. Affective defense behavior elicited from the midbrain central gray is characterized by marked vocalization such as hissing and growling, pupillary dilatation, urination and piloerection. In contrast, quiet biting attack elicited from the midbrain central gray lacks overt autonomic signs observed with affective defense response as well as the stalking component which is typically associated with stimulation of the lateral hypothalamus. Nevertheless, central gray-elicited attack resulted in a directed bite of the neck of an anesthetized rat in a manner similar to that observed from the hypothalamus. Affective defense was elicited from the dorsal half of the midbrain central gray, while quiet biting attack was obtained following stimulation of the ventral half of the midbrain central gray, thus indicating a functional differentiation of the central gray with respect to these two forms of aggression. In a separate series of experiments, affective defense or quiet biting attack response was identified by electrical stimulation through a cannula electrode situated in the midbrain central gray. The affective defense responses were subsequently elicited following microinjections of D,L-homocysteic acid through the same cannula electrode in order to demonstrate that these responses were the result of direct stimulation of cell bodies within the central gray. Then, one of the following autoradiographic tracing procedures was utilized: (1) [3H]leucine was injected through a cannula electrode and the animal was sacrificed after a 4- to 14-day survival period; or (2) a 2-DG solution was systemically injected and electrical stimulation was applied through the cannula electrode in order to metabolically activate the pathways associated with each of these responses. In general, the pattern of labelled target regions as indicated by 3H-amino acid radioautography was similar to that obtained from the 2-DG autoradiographic analysis. The principal ascending pathway associated with affective defense was traced to the anteromedial hypothalamus and medial thalamus. Concerning descending projections, label was traced into the central tegmental fields of the midbrain and pons, locus coeruleus and motor and main sensory nuclei of the trigeminal complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1987

The effects of intrahypothalamic injections of norepinephrine upon affective defense behavior in the cat.

The effects of norepinephrine microinjected into the anterior hypothalamus were examined in feline affective defense behavior elicited by electrical stimulation of the region of the ventromedial nucleus. Anterior hypothalamic sites from which affective defense behavior could also be elicited by electrical stimulation and which are known to receive inputs from both the ventromedial nucleus and brainstem noradrenergic neurons were selected for pharmacological analysis. Intracerebral injections of 250 ng (1 nM) and 500 ng (2 nM) quantities of norepinephrine placed into the anterior hypothalamus resulted in a significant lowering of the attack thresholds. These reductions in response thresholds which were reversed by either pre- or post-treatment with yohimbine, indicate that the noradrenergic system may play an important role in the regulation of affective defense behavior.

Aggression↗

PubMed1986

Effects of experimental temporal lobe seizures upon hypothalamically elicited aggressive behavior in the cat.

An experiment was performed in order to determine the effects of temporal lobe seizures upon hypothalamically elicited aggressive behavior in the cat. Seizures were induced by electrical stimulation of the pyriform cortex or those subnuclei of the amygdala which had previously been shown to modulate aggressive responses at subseizure current levels. The results clearly indicate that a significant modification of affective defense thresholds following seizures was a direct function of the locus of stimulation. Specifically, seizures generated from the pyriform cortex and medial aspects of the amygdala (sites associated with prior facilitation of affective defense as determined by subseizure electrical stimulation) were followed by a reduction in threshold for this response. In contrast, an elevation in affective defense thresholds occurred when seizures were generated from the central or lateral nuclei of the amygdala (sites associated with prior suppression of affective defense as determined by subseizure electrical stimulation). The primary pathway utilized in the facilitation of affective defense appears to involve the stria terminalis, its bed nucleus, and the anterior medial hypothalamus. Preliminary data suggest that seizures generated from the pyriform cortex or amygdala can also modify quiet biting attack behavior, but in a manner opposite to that demonstrated for affective defense.

Aggression↗

PubMed1986

Regulation of feline aggression by the bed nucleus of stria terminalis.

The purpose of this experiment was to study the possible modulatory role of the bed nucleus of stria terminalis (BNST) in the regulation of affective defense and quiet biting attack reactions in the cat. The experimental paradigm employed concurrent electrical stimulation of the hypothalamic attack sites and of the BNST. The results of the present study demonstrate that concurrent electrical stimulation of the BNST can differentially modulate the two different forms of aggressive behavior by facilitating affective defense and by suppressing quiet biting attack.

Aggression↗

PubMed1985

Topographically organized midbrain modulation of predatory and defensive aggression in the cat.

Hypothalamic sites from which quiet biting attack and affective defense were elicited, were concurrently stimulated with others in the midbrain from which modulation of these behaviors was attempted. Stimulation of medial and lateral aspects of the tegmentum differentially modulated quiet biting attack and affective defense behavior. Facilitation of quiet attack and suppression of affective defense resulted from stimulation of the lateral tegmentum, while suppression of quiet attack and facilitation of affective defense followed stimulation of its medial aspect.

Aggression↗

PubMed1985

Differential control of hypothalamically elicited flight behavior by the midbrain periaqueductal gray in the cat.

The purpose of the present study was to determine the role of the midbrain periaqueductal gray (PAG) and thalamic centrum medianum-parafascicular complex (CM-Pf) in the regulation of hypothalamically elicited flight behavior in the cat. The experimental paradigm involved a comparison of the differences in response latencies between single stimulation of the hypothalamus and concurrent stimulation of the hypothalamus and sites in the PAG or the CM-Pf. Dual stimulation of the ventral and dorsal aspects of the PAG resulted in differential modulation of flight behavior. Stimulation of the dorsal PAG suppressed hypothalamically elicited flight behavior while stimulation of the ventral aspects of the PAG facilitated flight behavior. Facilitation of flight behavior was also found from stimulation of ventral portions of the CM-Pf.

Animals↗

PubMed1985

Forebrain structures regulating flight behavior in the cat.

The present study was conducted to determine the role of the bed nucleus of the stria terminalis (BNST) and preoptic region in the regulation of hypothalamically elicited flight behavior in the cat. The general paradigm involved concurrent electrical stimulation of sites in the hypothalamus from which flight responses were elicited and of the BNST or preoptic region from which modulation of flight behavior was attempted. Electrical stimulation of the dorsal and ventral preoptic region modulated flight behavior in opposing ways. Suppression of flight behavior resulted from stimulation of the BNST and ventral aspect of the preoptic region, while facilitation of the behavioral response followed stimulation of the dorsal aspect of the preoptic region.

Animals↗

PubMed1984

An analysis of the mechanisms underlying septal area control of hypothalamically elicited aggression in the cat.

This experiment was performed in order to examine several of the underlying mechanisms by which the septal area and adjacent regions regulate quiet biting attack behavior elicited from electrical stimulation of the hypothalamus in the cat. The results clearly indicate that stimulation of the septal area and anterior cingulate gyrus increased the latency for the occurrence of quiet biting attack behavior. Those sites within the septal area from which inhibition of attack can be produced are linked to sensory mechanisms associated with trigeminal reflexes activated during hypothalamic stimulation. Stimulation of these septal area sites decreased the lateral extent of the 'effective sensory fields' of the lipline established during hypothalamic stimulation, but did not appear to have any affect upon the latency of the hypothalamically elicited jaw-opening response. Deoxyglucose autoradiography revealed that the inhibition resulting from stimulation of the lateral septal area may be due to either the monosynaptic activation of the lateral hypothalamus or the disynaptic activation of this area utilizing a circuit involving the nuclei of the diagonal band of Broca.

Aggression↗

PubMed1984

A [14C]2-deoxyglucose analysis of the functional neural pathways of the limbic forebrain in the rat. IV. A pathway from the prefrontal cortical-medial thalamic system to the hypothalamus.

The present study utilized the [14C]2-deoxyglucose (2-DG) cell labeling procedure to characterize a functional pathway from the prefrontal cortex (Pfc) and mediodorsal thalamic nucleus (MD) to the hypothalamus. Rats were injected with 2-DG prior to a 45 min experimental paradigm consisting of alternating 30 s on-off periods of electrical brain stimulation. Standard procedures were utilized for the removal and processing of brain tissue for X-ray autoradiography. In the first phase of this study, stimulation applied to the prefrontal cortex generally yielded a pattern of 2-DG distribution consistent with the findings of classical anatomical studies. Stimulation of the dorsomedial and ventromedial prefrontal cortex or the infralimbic cortex produced the most effective activation of the diencephalon. This activation was primarily limited to MD, with no involvement of any region of the hypothalamus. In the second phase of this study, brain regions activated following stimulation of sites along the rostro-caudal axis of MD were examined. Stimulation of MD resulted in the activation of the nucleus reuniens and other midline and non-specific thalamic nuclei. Stimulation of this nucleus also activated the ventromedial thalamic nucleus, medial aspects of the nucleus accumbens and the medial and sulcal prefrontal cortices. Again, in each of these cases, labeling within any region of the hypothalamus could not be detected. Since MD stimulation activated the midline thalamus, and the nucleus reuniens in particular, the last phase of this experiment involved stimulation of the nucleus reuniens in order to determine the source of medial thalamic inputs to the hypothalamus. Stimulation of the nucleus reuniens activated fibers which were distributed to both the medial and lateral hypothalamus. In addition, stimulation also activated the descending periventricular system, which could be followed to the level of the midbrain central gray and such limbic structures as the hippocampal formation, septal area, amygdala and prefrontal cortex. These findings indicate that Pfc-MD activation of the hypothalamus is achieved indirectly via interneurons within the nucleus reuniens.

Animals↗