NEUROCHEMICAL MECHANISMS UNDERLYING AMYGDALOID MODULATION OF AGGRESSIVE-BEHAVIOR IN THE CAT

Citation
A. Siegel et al., NEUROCHEMICAL MECHANISMS UNDERLYING AMYGDALOID MODULATION OF AGGRESSIVE-BEHAVIOR IN THE CAT, Aggressive behavior, 21(1), 1995, pp. 49-62
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Psychology,"Behavioral Sciences
Journal title
ISSN journal
0096-140X
Volume
21
Issue
1
Year of publication
1995
Pages
49 - 62
Database
ISI
SICI code
0096-140X(1995)21:1<49:NMUAMO>2.0.ZU;2-9
Abstract
Studies designed to determine the respective roles of substance P, exc itatory amino acids, and enkephalins in amygdaloid modulation of defen sive rage behavior in the cat are presented. The basic design of these studies involved three stages. In stage I, cannula electrodes for sti mulation and drug infusion were implanted into medial hypothalamic or midbrain periaqueductal gray (PAG) sites from which defensive rage beh avior could be elicited. Then, a stimulating electrode was implanted i nto a site within the medial, basal, or central nuclear complex from w hich modulation of the defensive rage response could be obtained. Amyg daloid modulation of defensive rage was determined in the following ma nner: it employed the paradigm of dual stimulation in which comparison s were made of response latencies between alternate trials of dual (i. e., amygdala + medial hypothalamus [or PAG]) and single stimulation of the hypothalamus or PAG alone. Thus, stage I established the baseline level of modulation (i.e., facilitation or suppression of defensive r age) in the predrug stimulation period. In stage II, a selective or no nselective receptor antagonist for a given transmitter system was admi nistered either peripherally or intracerebrally at the defensive rage site, after which time the same dual stimulation paradigm was then rep eated over the ensuing 180 min postinjection period in order to determ ine the effects of drug delivery upon amygdaloid modulation of defensi ve rage. Stage III of the study took place at the completion of the ph armacological testing phase. The retrograde axonal tracer, Fluoro-Gold , was microinjected into the defensive rage site within the medial hyp othalamus or FAG, and following a 6-14 day survival period, animals we re sacrificed and brains were processed for histological and immunocyt ochemical analyses for the neurotransmitters noted above. This procedu re thus permitted identification of cells within the amygdala which we re labeled retrogradely and which were also immunostained positively f or substance P, excitatory amino acids, or enkephalin. For studies inv olving substance P, defensive rage was elicited from the medial hypoth alamus and for studies examining the roles of excitatory amino acids a nd enkephalin, defensive rage was elicited from the PAG. In the first study, facilitation of hypothalamically elicited defensive rage was ob tained with dual stimulation of the medial nucleus of the amygdala. In separate experiments, the selective NK1 non-peptide antagonist, CP 96 ,345, was administered both peripherally as well as intracerebrally in to the hypothalamic defensive rage sites in doses of 0.5-4.0 mg/kg (i. p.) and 0.5-2.5 nmol (i.c.). Following drug delivery, the facilitatory effects of medial amygdaloid stimulation were blocked in a dose and t ime-dependent manner in which the effects were noted as early as 5 min postinjection. The maximum drug dose (4.0 mg/kg) employed for periphe ral administration resulted in a 42% reduction in the facilitatory eff ects of the medial amygdala (P < 0.002). This drug, when microinjected directly into medial hypothalamic defensive rage sites at the maximum dose level of 2.5 nmol, resulted in an 84% reduction of the suppressi ve effects of amygdaloid stimulation (P < 0.5) at 5 min postinjection. In the next study, an N-methyl-D-aspartate (NMDA) antagonist, DL-alph a-amino-7-phosphonoheptanoic acid (AP-7), was administered either peri pherally (0.1-1.0 mg/kg) or intracerebrally (0.2 and 2.0 nmol) into FA G defensive rage sites. Facilitation of defensive rage behavior, which was observed following dual stimulation of the basal amygdala and FAG , was significantly reduced by either route of drug administration in a dose- and time dependent manner At the maximum dose level of periphe ral administration, AP-7 reduced amygdaloid facilitation of defensive rage by 63% (P < 0.001) for 60 min, postinjection. A smaller (i.e., 19 %) but still significant (P < 0.05) reduction in facilitation was obta ined following intracerebral administration of the drug. In a third st udy, the non-selective opioid receptor antagonist, naloxone (27.5 nmol ), infused directly into FAG defensive rage sites, totally blocked the suppressive effects of central amygdaloid stimulation for a period of 30 min (P < 0.05) in a dose- and time dependent manner. The anatomica l phase of this study revealed the following relationships: 1) that la rge numbers of neurons projecting to the medial hypothalamus from the medial amygdala immunoreact positively for substance P; 2) that neuron s projecting to the FAG from the basal complex of amygdala immunoreact positively for glutamate and aspartate; and 3) that neurons located w ithin the central nucleus of the amygdala which project to the FAG imm unoreact positively for met-enkephalin. Collectively, these observatio ns provide new evidence which characterizes the likely neurotransmitte rs linked with specific amygdaloid pathways subserving the modulation of defensive rage behavior in the cat. (C) 1995 Wiley-Liss, Inc.