A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does not contribute to the development of the observed hyperalgesia. Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws and these latency changes corresponded to a decreased thermal nociceptive threshold. Both the thermal method and the Randall-Selitto mechanical method detected dose-related hyperalgesia and its blockade by either morphine or indomethacin. However, the thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold.

A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.

The ascending monoamine pathways in the rat brain are demonstrated by the pile up of fluorescent material occurring in the axons after various types of lesions. The anatomy of the pathways is outlined in drawings of frontal sections of the brain and the origin and termination of several pathways is determined by studying the anterograde and retrograde degeneration occurring after well localised lesions. It is possible to separate the ascending NA pathways into a dorsal and a ventral bundle of axons. The dorsal bundle innervates the cortex and the hippocampus and the ventral bundle supplies NA nerve terminals to the medulla, the pons, the mesencephalon and the diencephalon. The dorsal bundle is found to originate in the locus coeruleus. Lesions of this nucleus abolish the nerve terminals in all cortical areas and in several other areas of the brain indicating a unique role for the locus coeruleus in influencing the activity of the entire brain. The 5-HT pathways have a distribution similar to the ventral NA pathyway. The course of the nigro-striatal and the meso-limbic DA pathways is presented in detail.

Stereotaxic mapping of the monoamine pathways in the rat brain.

Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations.

The sections in this article are:


1
Essence of Prefrontal Function: Regulation of Behavior by Representational Knowledge
11
Subdivisions of Prefrontal Cortex

12
Global Nature of Prefrontal Syndrome in Humans

13
Animal Model for Prefrontal Function in Humans

14
Delayed-Response Tests and Varying Interpretations of Their Functional Significance

15
Distractability and Perseveration: Secondary Consequences of Basic Defect in Representational Memory

16
Representational Memory in Wisconsin Card Sort and Other Diagnostic Tests of Prefrontal Function in Humans

17
Localization of Delayed-Response Function: Principal Sulcus

18
Circuit Basis of Visuospatial Functions




2
Accessing and “On-Line” Processing of Representations in Visuospatial Domain: Parietal-Prefrontal Connections
21
Visuospatial Representational Memory in Humans

22
Spatial-Mnemonic Nature of Delayed-Response Deficit: Domain-Specific Memory Loss

23
Topography of Representational Memory in Prefrontal Cortex

24
Electrophysiological Evidence of Spatial-Mnemonic Processes in Principal Sulcus

25
Parietal-Prefrontal Connectivity

26
Columnar and Laminar Framework for Feedforward and Feedback Mechanisms

27
Functional Significance of Parietal-Prefrontal Collaboration




3
Long-Term Memory and “Off-Line” Processing: Prefrontal-Limbic Connections
31
Role of Hippocampus in Spatial Memory

32
Multiple Connections Between Principal Sulcus and Hippocampal Formation

33
Quadripartite Neural Network: Parietal-Temporal-Cingulate-Prefrontal Circuit

34
Limbic Contribution to Spatial Memory




4
Response Initiation and Inhibition: Projections to Striatum, Tectum, Thalamus, and Premotor Cortex
41
Motor-Control Functions of Prefrontal Cortex

42
Cortical-Striatal Pathway and Related Feedback Loops

43
Cortical-Tectal Pathway

44
Thalamic-Cortical Systems

45
Prefrontal-Premotor Connections: Anterior Supplementary Motor Cortex Relays

46
Functional Speculations




5
Modulatory Mechanisms: Brain Stem Catecholamine Projections
51
Activation of Cognitive Machinery

52
Concentration and Synthesis of Catecholamines in Primate Cortex

53
Brain Stem Innervation of Prefrontal Cortex

54
Delayed-Response Deficits and Recovery Produced by Catecholamine Loss and Replacement in Prefrontal Cortex

55
Circuit Basis for Neuromodulation in Principal Sulcus




6
Multiple Subsystems of Prefrontal Cortex: Unity or Diversity of Function
61
Unity or Diversity of Prefrontal Function

62
Frontal Eye Fields

63
Inferior Convexity

64
Orbital Prefrontal Cortices

65
Problem of Integration




7
Diseases Affecting Prefrontal Cortex
71
Schizophrenia: Loss of Corticocortical Processing and Regulation of Behavior by Representational Knowledge

72
Wernicke-Korsakoff Syndrome: Loss of Thalamocortical and Brain Stem Modulatory Mechanisms

73
Huntington's Chorea and Parkinson's Disease: Loss of Prefrontal-Striatal Mechanisms and Initiation or Inhibition of Motor Response

74
Overview of Neurobiology of Disease




8
Summary

Circuitry of Primate Prefrontal Cortex and Regulation of Behavior by Representational Memory

The urinary excretion of catecholamines has been measured in 32 patients with disorders of the basal ganglia. Sixteen patients with Parkinsonism (idiopathic, postencephalitic, and arteriosclerotic types) had a significantly lower amount of dopamine in the urine during a 24-hour period than a group of 24 normal control subjects. In a group of 16 patients with various striatal syndromes the excretion of dopamine and epinephrine was significantly higher than normal. Norepinephrine excretion was similar in the three groups. The lowest mean value of urinary dopamine was found in postencephalitic Parkinsonism; the highest occurred in Wilson's disease.

https://science.sciencemag.org/content/sci/133/3465/1706.2.full.pdf

Excretion of Dopamine in Diseases of Basal Ganglia

Monoamine metabolites in lumbar CSF: The question of their origin in relation to clinical studies

Apomorphine hydrochloride was administered sc to 12 adult men on 23 occasions. In doses of 0.75–1.0 mg, apomorphine-HCl increased the concentration of growth hormone (GH) in serum above 10 ng/ml in all 12 subjects; peak values occurred at 30–60 min following injection. The increase was antagonized in the 4 subjects pretreated with chlorpromazine. Apomorphine decreased serum prolactin (PRL) levels in 4 subjects but only in a dose of 1.0 or 1.5 mg; the compound failed to decrease chlorpromazineinduced elevated levels of PRL. The drug had no effect on serum LH or FSH. These results are compatible with modulation of GH secretion by a dopaminergic mechanism. Further studies are needed to determine the reliability and potential clinical usefulness of apomorphine as an agent to stimulate GH secretion.

Effect of apomorphine on growth hormone, prolactin, luteinizing hormone and follicle-stimulating hormone levels in human serum.

• Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent pattern of correlation was found for COMT and TH. Mean MAO activity was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/491655/archpsyc_34_1_009.pdf

Theodore L. Sourkes

Papers

Excretion of Dopamine in Diseases of Basal Ganglia

Monoamine metabolites in lumbar CSF: The question of their origin in relation to clinical studies

Effect of apomorphine on growth hormone, prolactin, luteinizing hormone and follicle-stimulating hormone levels in human serum.

Monoamine metabolism in human brain.

Effect of apomorphine on human-growth-hormone secretion