Curt A. Sandman

Polypeptide influences on attention, memory and anxiety in man ☆ ☆☆

Abstract The effects of two polypeptides, ACTH 1–24 and ACTH 4–10 on a variety of bioelectric and behavioral measures of attention, memory and anxiety in human subjects were examined within the context of a disjunctive reaction time paradigm. ACTH 1–24 had no effect on any of the measures involved; ACTH 4–10 , however, served to improve visual memory, decrease anxiety, reinstitute a previously habituated alpha blocking response in the occipital EEG, and generally influence the occipital EEG toward a pattern consistent with increased attention. The results were taken to suggest a direct polypeptide influence on CNS attentional mechanisms.

Enhancement of attention in man with ACTH/MSH 4-10.

Normal men were infused for 4 hr with ACTH/MSH 4-10 or a control solution. Behavioral testing after the infusion indicated that subjects who received ACTH/MSH 4-10 were less anxious and had better visual memory than control subjects but the predominant effect of the heptapeptide was to increase visual attention. It was speculated that ACTH/MSH 4-10 may be uniquely coded for attentional functioning.

Effect of naloxone on analgesia induced by food deprivation

Abstract Naloxone (4 mg/kg) or saline was administered to animals under food deprived and non-deprived conditions prior to testing pain sensitivity in the tail flick test. Food deprived animals exhibited significantly elevated latencies in comparison to latencies observed under non-deprived conditions. This analgesia was diminished by treatment with the opiate receptor antagonist, naloxone. These findings suggest that analgesia induced by food deprivation is mediated in part by opiate receptor systems.

Neuroendocrine influences on visual discrimination and reversal learning in the albino and hooded rat

Abstract Pigmented and nonpigmented rats were treated with MSH and MRIH-I and tested on a brightness discrimination and reversal task. Pigmented rats acquired the original habit and performed the reversal task significantly faster than albino rats. MSH and MRIH-I administration significantly facilitated reversal learning performance. Simple effects tests indicated that the effects of MSH and MRIH-I were significant only for albino rats on the reversal task. The data were interpreted to suggest that MSH and MRIH-I affects attentional processes more profoundly in visually deficient animals.

PHYSIOLOGICAL DIFFERENTIATION OF SENSORY AND COGNITIVE TASKS AS A FUNCTION OF WARNING. PROCESSING DEMANDS, AND REPORTED UNPLEASANTNESS *

Low and highly stressful sensory tasks (viewing slides of autopsy) were employed to assess the effects of stressful stimuli that required a minimal amount of cognitive elaboration. Cognitive (arithmetic, anagram, and digit-string memorization) tasks each at two levels of difficulty were matched for reported unpleasantness with autopsy slides to provide stimuli in which stress reactions were constant but cognitive processing requirements varied. Heart rate, skin potential level, and skin potential responses were monitored. Thirty-two subjects received two presentations of each type of task, one each of which was preceded by a warning signal. The results indicated that heart rate accelerated during cognitive tasks and decelerated during slide presentations of autopsy; the warning signal accentuated the heart-rate pattern associated with the task. Analyses of individual tasks revealed that heart rate was greater during the performance of difficult (more cognitively demanding) than easy cognitive tasks but that heart rate was not affected by the reported unpleasantness of the autopsy slides. Skin potential responses were more evident during the presentation of stressful (unpleasant) stimuli for both cognitive and sensory tasks; skin potential level, however, differentiated neither the tasks nor the stressfulness of stimuli within the tasks. These results are interpreted as being consistent with Laceys hypothesis concerning cognitive elaboration, cardiac activity, and response patterning.

Neuropeptide MSH/ACTH 4-10 enhances attention in the mentally retarded.

Twenty adult mentally retarded men were randomly assigned to receive MSH/ACTH 4-10 or a vehicle control solution in a double blind procedure. After an intravenous injection the subjects were presented with an orienting sequence and a series of behavioral tests. Treatment with the peptide resulted in a significant decelerative heart rate response during the test stimulus of the orienting sequence. Improved performance of the intradimensional and extradimensional shift of a visual discrimination procedure was significant for subjects receiving MSH/ACTH 4-10. The pattern of response on the subproblem analysis of the extradimensional shift reflected greater dimensional attention in the subjects treated with the peptide. Attentive subjects given MSH/ACTH 4-10 evidenced significant improvement on a rhythm matching test, a test of spatial localization and a visual retention test. The data were interpreted as indicating that the peptide resulted in improved attention of stimulus processing. It was speculated that MSH/ACTH 4-10 may be unquely coded for perceptor/attentional functioning and may be useful as a treatment for disorders of attention.

Behavioral influences of the neuropeptides ACTH and MSH: A methodological review

Abstract During the past 20 years, there has been repidly accumulating evidence that polypeptide hormones of pituitary origin are important mediators of behavior. The research has been focused primarily upon the actions of adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (MSH). A large number of methodological difficulties have developed and are in need of careful review. Important pharmacological and behavioral variables are reviewed both in general and as they relate to current research on the actions of ACTH and MSH. In addition, suggestions are given for control and/or study of these variables. Finally, the main integrating hypotheses, fear, memory and attention, are reviewed and evaluated.

Effects of MSH/ACTH 4–10 on memory, attention and endogenous hormone levels in women☆

Abstract Young women, tested during their menstrual phase or at midcycle, received either 30 mg MSH/ACTH 4–10 or the saline diluent subcutaneously in a doubleblind procedure. Behavioral testing indicated that the peptide significantly facilitated verbal memory and impaired reversal learning ability. Visual memory, field independence, basal heart rate and state anxiety were not influenced by the treatment. Radioimmunoassays of plasma samples collected across the testing period indicated that levels of LH, FSH, 17-β-estradiol, progesterone and cortisol were not significantly altered by the peptide. It was speculated that human sex differences in response to MSH/ACTH 4–10 exist with females exhibiting an enhancement of verbal modalities.

The effects of neonatal injections of α-MSH on the open-field behavior of juvenile and adult rats

Male and female infant albino rats, between the ages of 2 and 7 days, were treated with either MSH or the vehicle solution and then tested in an open-field apparatus when they were 45 days old and again when they were 120 days old. Treatment with α-MSH resulted in greater body contact of adult males both at 45 and at 120 days of age. Females treated with α-MSH exhibited greater body contact when tested at 45 days of age, but did not display increased body contact when tested at 120 days of age. These results are indicative of a sex difference in response to neonatal administration of α-MSH.

Effects of neonatal cerebral ventricular injection of ACTH 4–9 and subsequent adult injections on learning in male and female albino rats

An investigation of permanent developmental effects of a potent, long acting ACTH/MSH 4-10 analogue (Organon 2766) on adult passive avoidance performance and of subsequent peripheral adult injections of the same substance on visual (black and white) discrimination learning and reversal in a Thompson-Bryant box was conducted. A subproblem analysis of visual and position preferences during reversal was performed. No differences in passive avoidance performance or in original discrimination learning were obtained. Both infant and adult treatments enhanced reversal learning and visual orientation (proportion of responese to the previously positive stimulus). Infant treatment suppressed position orientation in males and enhanced position orientation in females. These effects were interpreted as indicating that ACTH-like peptides enhance attention to the relevant stimulus by a direct effect on the brain.