Enhancement of basal and pentylenetetrazol (PTZ)-stimulated dopamine release in the brain of freely moving rats by PTZ-induced kindling

The effects of pentylenetetrazol (PTZ)-induced kindling on the activity of mesocortical, mesoaccumbens, and nigrostriatal dopaminergic neurons was investigated with the transversal microdialysis technique in freely moving rats. Four days after the last chronic administration of PTZ, the basal extracellular concentrations of dopamine in the prefrontal cortex, nucleus accumbens, and striatum of kindled rats were significantly increased (+76, +36, +49%, respectively) relative to those of animals chronically treated with saline. Moreover, dopamine output was markedly more sensitive to the effect of a challenge injection of PTZ (20 mg/kg ip) in the prefrontal cortex (+93 vs. +50%, relative to basal values), the nucleus accumbens (+36 vs. +4%), and the striatum (+50 vs. +35%) of kindled rats relative to that in the control animals. Because kindled rats and their controls are habituated to handling, the neurochemical mechanisms that underlie the effects of chemical kindling on the sensitivity of dopaminergic neurons to PTZ were investigated by comparing the effects of an acute administration of PTZ (20 mg/kg ip) between naive and handling-habituated animals. The sensitivity of dopamine output to PTZ in naive rats was markedly greater than that in handling-habituated animals for the prefrontal cortex (+83 vs. +50%) and nucleus accumbens (+35 vs. +4%), but not for the striatum (+35 vs. +32%). These results indicate that PTZ kindling enhances the basal activity and the sensitivity to PTZ of dopamine neurons in rat brain and suggest that mesocortical, mesoaccumbens, and nigrostriatal dopaminergic neurons contribute to the central alterations associated with experimental epilepsy. Synapse 26:351–358, 1997. © 1997 Wiley-Liss Inc.     

Amygdala and pyriform cortex kindling in vasopressin deficient rats (Brattleboro strain)

Homozygous and heterozygous Brattleboro rats and Long--Evans control rats were subjected to repeated electrical stimulation of the amygdala or pyriform cortex in a kindling paradigm. The homozygous Brattleboro group stimulated in the amygdala was retarded in its kindling rate relative to heterozygous Brattleboros and Long--Evans controls. The retarded kindling rate of the homozygous Brattleboros stimulated in the amygdala is attributed to a delay in seizure development at stages 1 and 2 which suggests that vasopressin may be necessary for normal kindling from the amygdala to take place.     

Sex-dependent effects of amygdaloid lesions on the social play of prepubertal rats

Male and female prepubertal rats, like many primate species, differ in the frequency with which they engage in social play (play-fighting); males engage in more social play than females. This sex difference in the rat has been found to be under the control of gonadal hormones acting during the neonatal period. In the present study we examined the effects of lesions of the amygdala, a prominent neuroendocrine control area, on the play-fighting of male and female prepubertal rats. Bilateral, electrolytic lesions and sham control treatments were made at 21 or 22 days of age and the animals were then observed daily in intact groups between 26 and 40 days of age. Amygdaloid lesions suppressed social play in male rats to levels that were indistinguishable from those of control females. In contrast to males, amygdaloid lesions had no effect on the social play of females. Sex differences in the anatomy and physiology of the amygdala are discussed as a possible explanation of its apparent differential influence on the social play of male and female prepubertal rats.     

Role of the hippocampus in development of the seizure syndrome induced by kindling stimulation of the caudate nucleus

Institute of Biomedical Technology, Ministry of Health of the USSR, Moscow (Presented by Academician of the Academy of Medical Sciences of the USSR G. N. Kryzhanovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 8, pp. 145–147, August, 1989.     

Measurement and characterization of neuronal cholecystokinin using a novel radioreceptor assay

This study describes a novel radioreceptor assay (RRA) for cholecystokinin (CCK) which is the first to measure and characterize brain CCK using a technique not dependent on the generation of peptide antibodies. The CCK RRA utilizes the mouse cerebral cortex CCK receptor as the binding source and [125I]BH-CCK-8 as the radiolabelled probe. [125I]BH-CCK-8 bound to the central CCK receptor with a Kd of 1.82 nM and a Bmax of 1.21 pmol/g tissue. Unlabelled CCK-8 displaced the specific binding of [125I]BH-CCK-8 with an inhibition constant of 3.84 nM. CCK was extracted (90% methanol) from discrete brain regions (mouse) and quantified using the CCK RRA. The amygdala contained the highest concentration of CCK (394 +/- 21 pmol/g tissue), followed by the olfactory bulbs (306 +/- 19 pmol/g tissue) and cerebral cortex (298 +/- 21 pmol/g tissue). Moderate levels of CCK were found in the hippocampus (212 +/- 18 pmol/g tissue), striatum (146 +/- 15 pmol/g tissue) and hypothalamus (129 +/- 9 pmol/g tissue). Low levels of CCK were recorded in the pons (45 +/- 5 pmol/g tissue), medulla (41 +/- 3 pmol/g tissue) and spinal cord (29 +/- 3 pmol/g tissue), whilst no CCK was detected in the cerebellum. The molecular forms of CCK in amygdala, cerebral cortex and hypothalamus were characterized using RRA in conjunction with HPLC. CCK-8 was identified as the major molecular form (88%, 94% and 91% of total CCK activity in amygdala, cortex and hypothalamus, respectively) with a smaller component attributable to CCK-4 (8%, 5% and 6% of the total CCK activity).     

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)