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Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal.

Corticotropin-releasing factor (CRF) has been implicated in the mediation of the stress-like and negative affective consequences of withdrawal from drugs of abuse, such as alcohol, cocaine, and opiates. This study sought to determine whether brain CRF systems also have a role in cannabinoid dependence. Rats were treated daily for 2 weeks with the potent synthetic cannabinoid HU-210. Withdrawal, induced by the cannabinoid antagonist SR 141716A, was accompanied by a marked elevation in extracellular CRF concentration and a distinct pattern of Fos activation in the central nucleus of the amygdala. Maximal increases in CRF corresponded to the time when behavioral signs resulting from cannabinoid withdrawal were at a maximum. These data suggest that long-term cannabinoid administration alters CRF function in the limbic system of the brain, in a manner similar to that observed with other drugs of abuse, and also induces neuroadaptive processes that may result in future vulnerability to drug dependence.

Amygdala↗

Involvement of the frontotemporal lobe and limbic system in amyotrophic lateral sclerosis: as assessed by serial computed tomography and magnetic resonance imaging.

The present paper concerns serial examinations of computed tomography (CT) and magnetic resonance imaging (MRI) in 22 patients with sporadic amyotrophic lateral sclerosis (ALS). Supranuclear ophthalmoplegia developed in 13 and dementia in 3 patients. The investigations showed gradually progressive atrophy, first in the frontal and anterior temporal lobes then in the precentral gyrus, and later in the postcentral gyrus, anterior part of the cingulate gyrus, corpus callosum and brain stem tegmentum. MRI revealed high intensity signals on T2-weighted images in the precentral and adjacent gyri, frontotemporal white matter and pyramidal tract as well as rarely in the globus pallidus and thalamus. These neuroradiological changes were not related to the duration of the clinical course or to the degree of the motor impairment. These alterations may play a critical role in the supranuclear ophthalmoplegia seen in ALS patients. The dementia of ALS probably reflects involvement of both the frontotemporal lobes and limbic system.

Adult↗

[Background activity of neurons of the cortical portions of the limbic system of the rabbit brain].

Background activity recorded extracellularly in cortical limbic areas of unanesthetised rabbits was analyzed by means of a computer. Special attention was payed to the rhythmic components of the activity in theta- and delta-range. Only small proportion of units (5-12%) in various structures, except lateral entorhinal cortex possessed rhythmic modulation in theta-range. Delta-modulation was observed in all investigated areas, but had various characteristics. It was very prominent both in subiculum (45% of units) and in entorhinal cortex (22%). While in subiculum (as in other areas) it consisted of high-frequency short bursts with long interburst intervals, the opposite was typical of entorhinal cortex. Arousing stimuli increased frequency and regularity of theta-bursts and desynchronized delta-activity in majority of structures; in entorhinal cortex they increased intraburst frequency of discharges without influencing frequency or regularity of the bursts.

Animals↗

Limbic system seizures and aggressive behavior (superkindling effects).

This study was done to further analyze the neural mechanisms underlying aggressive behavior associated with psychomotor or temporal lobe seizures. The studies revealed that superkindling the aggressive system by sequential stimulations at seizure-inducing thresholds, of two or more sites in the limbic, hypothalamic, and basal ganglia structures facilitated the production of aggressive seizures. Aggressive behavior in the freely moving cat was evaluated in relation to the occurrence of hissing and growling during stimulation, after-discharge and postictal period. The behavior was correlated with the frequency of the elicited seizures and the seizure durations. Aggression did develop as a component behavioral manifestation of the limbic (psychomotor) seizure. Development of aggressive seizures was facilitated by "priming" the aggressive system. Optimum levels of aggressive behavior occurred with seizures of medium duration. Catecholamine blockers tended to attentuate the occurrence of aggression, whereas the agonist tended to facilitate it. Once the aggressive system was rendered hyperexcitable, exteroceptive stimuli also evoked aggressive attack behavior. It was concluded that repeatedly recurring limbic system seizures through superkindling mechanisms can eventually render the limbic-basal ganglia-preoptico-hypothalamic aggressive system hyper-responsive to both recurring seizures and to exteroceptive stimuli with resulting aggressive behavior with or without an accompanying seizure.

Aggression↗

Specific stimulus-evoked violent action in psychotic trigger reaction: a seizure-like imbalance between frontal lobe and limbic systems?

A recently proposed diagnostic class, psychotic trigger reaction, is deduced from careful clinical studies of eight white men, who upon a very specific trigger stimulus committed murder or attempted to (and in one case also rape). The new class is defined as a sudden ego-alien, motiveless (at least with respect to aggression), motor-wise well organized, violent complex action without emotional concomitants. The action is evoked (not provoked) by an individually unique stimulus within a specific context reviving repeated past traumatic experience. Typically there is no (significant) loss of consciousness and practically full recall. Observed are first-time hallucinations (visual, auditory, tactile, somesthetic, but not olfactory as in temporal lobe epilepsy) and signs of imbalance in the autonomic nervous system (loss of bladder control, ejaculation, profuse sweating, nausea). Only four of these men had previous psychiatric diagnoses (and then various ones) or abnormal EEGs at some time in their lives. Variety in prior diagnoses would be consistent with a seizure-like disorder, here specifically implicating an imbalance in functioning between limbic and frontal lobe systems. Clinical tests for the latter were prevailingly indicative of dysfunctioning. A detailed clinical analysis of the violent acts within their context suggests behaviors are analogous to certain limbic system mechanisms, especially the kindling phenomenon.

Adolescent↗