p-chlorophenylalanine-induced serotonin depletion: reduction in exploratory locomotion but no obvious sensory-motor deficits.

Para-chlorophenylalanine (PCPA) depletes central serotonin (5-hydroxytryptamine, 5-HT) by inhibiting tryptophan hydroxylase, an enzyme necessary for the synthesis of 5-HT. The effects of a wide range of PCPA doses (150-1000 mg/kg) on spontaneous exploratory locomotor activity in a novel environment, activity in running wheels and a number of sensory-motor capacities were examined. Administration of 1000 mg/kg PCPA reduced whole brain levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid to 9.4 and 8.2% of control levels, respectively. Treatment with PCPA produced a dose-dependent decrease in exploratory locomotion in an unfamiliar automated open field relative to vehicle-treated animals. Further, all measures of general, horizontal and vertical activity were suppressed by PCPA treatment. In contrast to previous work, hyperactivity of rats chronically housed in cages with running wheel access was not observed. In their home cages, some PCPA-treated rats exhibited hyper-reactivity to cutaneous stimulation. No other sensory-motor deficits were apparent. Previous theories of 5-HT function state that its action may be to inhibit motor activity or promote sleep. The present results challenge this view and suggest that 5-HT, at least in certain environments, may stimulate locomotor activity without directly controlling various sensory-motor capacities in rats.

Phenoxybenzamine reduces mortality associated with intracerebral injections of excitatory neurotoxins.

Intracerebral injections of kainic acid produce gross hematuria, renal cortical necrosis, and an associated high mortality. Hematuria is virtually eliminated and mortality significantly reduced by pretreatment with phenoxybenzamine.

Intracortical grafts of embryonic basal forebrain tissue restore low voltage fast activity in rats with basal forebrain lesions.

Unilateral injections of kainic acid into the basal forebrain in a series of rats resulted in an increase in large amplitude slow waves, a correlated burst-suppression pattern of multi-unit activity, and a decrease in acetylcholinesterase staining in the neocortex ipsilateral to the kainic acid injection. Subsequently, a cell suspension, prepared from rat embryonic basal forebrain tissue, was injected adjacent to the recording electrodes ipsilateral to the kainic acid injection. This produced a gradual recovery of low voltage fast activity (LVFA) and a correlated continuous discharge pattern of multi-unit activity in the neocortex ipsilateral to the kainic acid injection. LVFA recovered more slowly at neocortical recording sites that received an injection of a cell suspension of hippocampal primordial cells or no injection at all. Acetylcholinesterase-positive fibers from the basal forebrain tissue invaded host cortex; no comparable outrgrowths were demonstrable in the hippocampal primordium tissue grafts. Restoration of cholinergic electrocortical activation may play an important role in the improvements in behavioral performance produced by basal forebrain grafts in the cortex in animals with basal forebrain lesions.

Neocortical and hippocampal electrical activity following decapitation in the rat.

It has been debated whether or not decapitation of conscious animals is a humane procedure. This problem may be clarified on the basis of recent research that has indicated that neocortical low voltage fast activity (LVFA) and hippocampal rhythmical slow activity (RSA) can result from activity in either the cholinergic corticipetal projections from the basal forebrain or the serotonergic corticipetal projections from the brainstem. These inputs appear to produce, respectively, atropine-sensitive LVFA and RSA and atropine-resistant LVFA and RSA. In waking animals, atropine-resistant LVFA and RSA occur only in close correlation with motor activities such as spontaneous changes in posture, walking or struggling (Type 1 behavior). Painful stimuli readily elicit both Type 1 behavior and LVFA and RSA in atropine-treated rats. Atropine-sensitive LVFA and RSA may occur in anesthetized as well as in conscious animals, but atropine-resistant LVFA and RSA are generally absent during anesthesia. In the experiments reported here, rats were decapitated: (1) in the normal waking state; (2) after pretreatment with atropine or scopolamine; or (3) following induction of anesthesia with ethyl ether. Clear hippocampal RSA and neocortical LVFA were observed in conditions 1 and 3 but not in condition 2. It is concluded: (A) that atropine-sensitive LVFA and RSA are not good indices of conscious perception of pain since these waveforms occur during anesthesia as well as in the waking state; and (B) that the cerebral reaction to decapitation does not resemble the usual cerebral reaction to painful stimuli. This is consistent with the view that decapitation is not inhumane.

Pathways through cingulate, neo- and entorhinal cortices mediate atropine-resistant hippocampal rhythmical slow activity.

Rats prepared with a lesion separating the entorhinal cortex from the neocortex and cingulate cortex displayed apparently normal hippocampal rhythmical slow activity (RSA) with a frequency of 6-12 Hz in both CA1 and dentate gyrus during Type 1 behavior (locomotion, head movements, changes in posture). Variations in the commissural average evoked potential (AEP) and increased power in the 30-100 Hz range (fast waves) also correlated with Type 1 behavior. Urethane did not abolish the RSA. However, systemic administration of atropinic drugs eliminated all RSA and eliminated or attenuated the Type 1 behavior-related variations in the AEP and fast waves. Thus, the normally present atropine-resistant RSA was eliminated by the cortical lesion while atropine-sensitive RSA remained intact. Removal of cingulate cortex alone was partially effective in suppressing atropine-resistant RSA but a lesion of the neocortex only, sparing cingulate cortex, had a minimal effect on it. Lesions of the amygdala, the anterior or medial thalamus or the cerebellum had little or no effect on atropine-resistant RSA. Previous work has shown that lesions of the entorhinal cortex or lateral hypothalamus eliminate atropine-resistant RSA. We suggest that atropine-resistant RSA is mediated by a somewhat diffuse pathway which traverses the hypothalamus, cingulate cortex, and neocortex before reaching the hippocampus via the entorhinal cortex.

Typical albino retinofugal projections despite severe congenital optic nerve malformations in adult albino rats.

Albino rats with severe congenital malformations of the optic nerves consisting of kinks, folds, or loops were examined for possible abnormal central visual projections using the Fink-Heimer method. No abnormal projections were seen in any of the visual areas studied.

Construction of wire leads and electrodes for use in slow wave recording in small animals.

Techniques are described for the construction of wire electrodes and leads for use in recording slow wave activity in chronic animal preparations. Advantages of the technique include durability, lightness and absence of significant interference with animal movement.

Behavior of the rat after removal of the neocortex and hippocampal formation.

After surgical removal of the neocortex and hippocampal formation, rats retained most of the movement patterns of locomotion, climbing, grooming, feeding, and fighting. However, forepaw immobility during swimming was abolished. Feeding behavior was suppressed temporarily but recovered partially. The distinctive postures of sleep and walking and a circadian rhythm of motor activity were retained. However, behaviors were often not performed at the appropriate time and place. The normal sequence of grooming behavior was disrupted; food hoarding and social behavior were essentially abolished. Removal of the neocortex alone had much the same effect as removal of neocortex and hippocampus together. Removal of hippocampus alone produced only a mild disruption of behavior. It is suggested that ascending nonspecific projections to the cerebral cortex play an important role in the moment-to-moment control of behavior but are not essential for the sleep-waking cycle.