Byron A. Campbell

Ontogeny of Adrenergic Arousal and Cholinergic Inhibitory Mechanisms in the Rat

With spontaneous activity as a measure of arousal, dose response curves were established for scopolamine and amphetamine administered to 10-, 15-, 20-, 25-, and 100-day-old rats. Amphetamine always increased activity, but scopolamine had no efect on younger rats, which suggests that adrenergic excitatory areas in the brainstem mature more rapidly than cholinergic inhibitory areas in the forebrain.

Serotonergic inhibition of catecholamine-induced behavioral arousal

Abstract Amphetamine-induced locomotor activity in rats was potentiated by treatment with p -CPA, a depletor of brain serotonin. At stronger doses, p -CPA and amphetamine acted synergistically to produce activity levels that were greater than would be expected if the effects of the two drugs were simply additive. Administration of 5-HTP, the precursor of serotonin, prevented this effect. When rats treated with p -CPA were given an acute injection of reserpine, there resulted a biphasic action, p -CPA enhanced the heightened locomotor activity that immediately follows acute reserpine, but the subsequent level of sedation was not affected. These findings suggest that there is a serotonergic inhibitory system controlling catecholaminergic arousal.

The role of catecholamines in behavioral arousal during ontogenesis.

Effect of catecholamine depletion on normal hyperactivity in the neonatal rat was examined. Both α-methyl-para-tyrosine and reserpine significantly depressed behavioral arousal at 15 days postpartum, the age of greatest excitability. Heightened activity could be restored in drug-treated animals by administration of l-Dopa. These results indicate that the ontogenetic hyperactivity effect is a result of accelerated catecholamine function.

Hippocampal control of behavioral arousal: duration of lesion effects and possible interactions with recovery after frontal cortical damage.

Abstract The effects of gross hippocampal aspiration were compared with those of frontal cortical lesions on wheel running and generalized activity of rats during control and arousal conditions. The rate of recovery of these functions was then measured in animals with hippocampal lesions or with combined hippocampal and frontal lesions. From these studies, it appears that the hippocampus shares arousal control functions with frontal cortex, that it is partially responsible for the recovery that has been reported to occur after frontal lesions, but does not itself recover after damage.

Potentiation of behavioral arousal after cortical damage and subsequent recovery

Abstract The effect of ablating the frontal cortex on the rats activity-response to amphetamine was tested across a wide range of dosages and following varying postoperative intervals. Removal of the frontal poles (but not posterior cortical lesions) greatly potentiated the normal increases in spontaneous activity caused by amphetamine, and this effect became significantly reduced with longer postoperative intervals. Frontal lesions by themselves did not produce any changes in daily activity. The results are interpreted as supporting the hypothesis that the frontal cortex normally serves to control changes in behavioral arousal, and showing that recovery of this brain function takes place following cortical destruction.

Role of the central nucleus of the amygdala in olfactory heart rate conditioning.

The role of the central nucleus of the amygdala on olfactory heart rate conditioning in the infant rat was investigated. The conditioned stimulus consisted of a 10-s presentation of grape juice odor that was immediately followed by a 0.5-s, 0.35-mA subcutaneous shock. A sensitization control group was also run. Three days prior to testing, Ss received either bilateral electrolytic lesions of the central nucleus of the amygdala, sham lesions, or were left unperturbed. Results show that damage to the central nucleus of the amygdala severely impaired olfactory heart rate conditioning but that it had no deleterious effect on the heart rate orienting response to that stimulus or on the heart rate unconditioned response to shock. Results are analogous to those in previous research on auditory heart rate conditioning and suggest that the central nucleus of the amygdala may constitute a necessary stage in the transduction of a conditioned stimulus into a cardiac conditioned response regardless of sensory modality.

Habituation of the forelimb-withdrawal response in neonatal rats.

The purpose of the present research was to examine the ontogeny of habituation in the neonatal rat, using the forelimb-withdrawal response. Thresholds and latencies of the response, changing patterns of responding to shock stimuli, and habituation of the response were studied in rats 3 to 15 days of age. It was found that although response thresholds do not change during this period of development, response latencies decrease and amplitudes increase. Three- and 6-day old pups remain active much longer following shock than do 10- and 15day-olds. When compared for habituation to different frequencies of stimulation, 3-day-old rat pups were found to be much more susceptible to habituation at low frequencies than 15-day-olds. Insertion of a simple intense shock in the habituation series produced marked dishabituation in the 3-day-olds but little or none in the 15-day-olds. This pattern of results was obtained regardless of the locus of the dishabituating shock. Analysis of response latencies showed that although 15-day-olds responded 2 to 3 times more quickly than 3-day-olds, both age groups responded more rapidly to a strong shock than to a weak one. During habituation, response amplitudes of both 3- and 15-day-old pups declined with no change in latency. Age-related differences in habituation were shown to be independent of differences in reactivity to shock and more likely due to the emergence of response sensitization.

Delayed development of fear-potentiated startle in rats.

The developmental emergence of fear-potentiated startle was examined in rats ranging in age from 16 to 75 days. In Experiment 1, a pure tone served as the conditioned stimulus (CS) and an acoustic startle pulse served as the unconditioned stimulus (US) for fear conditioning. Fear-potentiated startle by the tone CS was observed in rats 23 days of age and older but not in rats 16 days of age. In Experiment 2, a light served as the CS. Rats 30 days of age and older showed fear-potentiated startle, whereas 23-day-old rats did not. The final experiment demonstrated that another behavioral index of fear, stimulus-elicited freezing, was observed earlier in development than fear-potentiated startle, confirming the effectiveness of the training procedure for conditioning fear. The results suggest that fear-potentiated startle is a relatively late-emerging response system, paralleling the development of conditioned autonomic changes (e.g., heart rate) rather than that of freezing.

The effect of para-chlorophenylalanine on aversion thresholds and reactivity to foot shock

Abstract The effect of para-chlorophenylalanine (p-CPA) on measures of sensitivity and reactivity to foot shock was investigated in the rat. Using a sensitive spatial preference technique, it was found that aversion-detection thresholds to foot shock were not changed by p-CPA. In another experiment, where the locomotor activity in response to various shock intensities was measured, it was found that foot shock produced significantly more activity in p-CPA treated animals at high shock levels but did not change the threshold shock level required to significantly increase activity. The data are interpreted to indicate that p-CPA does not change sensitivity to foot shock, but rather induces change in the reactivity of the organism to intense aversive stimulation.

Ontogeny of long-term memory for learned taste aversions.

Eighteen-day-old and adult rats were trained on a learned taste-aversion (illness reinforced) or a lick-suppression (shock reinforced) task and tested for retention after either 1, 28, or 56 days. Young rats showed a retention deficit relative to adults in the lick-suppression task but not for taste-aversion learning. Young rats did, however, show relatively less suppression to the saline solution than adult, but a follow-up experiment showed that changing the poisoned solution to a more-distinctive flavor produced high levels of suppression and no retention deficit in 18-day-old rats. In the final experiment a technique was developed for studying retention of taste aversion in suckling rats. Retention of taste aversion was studied in 10-, 12-, 15-, and 20-day-old rats at retention intervals ranging from 1 to 10 days. Using this procedure the younger (10- and 12-day-old) rats showed more rapid forgetting than 15- or 20-day-olds. These findings were interpreted as (I) evidence for a dissociation of memory for learned taste aversions from other kinds of learning and (2) further support for the general proposition of improved long-term memory during early ontogenesis.