Caffeine is the most widely consumed behaviorally active substance in the world. Almost all caffeine comes from dietary sources (beverages and food), most of it from coffee and tea. Acute and, especially, chronic caffeine intake appear to have only minor negative consequences on health. For this

Actions of Caffeine in the Brain with Special Reference to Factors That Contribute to Its Widespread Use

Nucleus locus ceruleus: new evidence of anatomical and physiological specificity

Preface .............................................................. 649

The functional states of the thalamus and the associated neuronal interplay.

This review is focused on purinergic neurotransmission, i.e., ATP released from nerves as a transmitter or cotransmitter to act as an extracellular signaling molecule on both pre- and postjunctional membranes at neuroeffector junctions and synapses, as well as acting as a trophic factor during development and regeneration. Emphasis is placed on the physiology and pathophysiology of ATP, but extracellular roles of its breakdown product, adenosine, are also considered because of their intimate interactions. The early history of the involvement of ATP in autonomic and skeletal neuromuscular transmission and in activities in the central nervous system and ganglia is reviewed. Brief background information is given about the identification of receptor subtypes for purines and pyrimidines and about ATP storage, release, and ectoenzymatic breakdown. Evidence that ATP is a cotransmitter in most, if not all, peripheral and central neurons is presented, as well as full accounts of neurotransmission and neuromodulation in autonomic and sensory ganglia and in the brain and spinal cord. There is coverage of neuron-glia interactions and of purinergic neuroeffector transmission to nonmuscular cells. To establish the primitive and widespread nature of purinergic neurotransmission, both the ontogeny and phylogeny of purinergic signaling are considered. Finally, the pathophysiology of purinergic neurotransmission in both peripheral and central nervous systems is reviewed, and speculations are made about future developments.

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Physiology and Pathophysiology of Purinergic Neurotransmission

Distribution of substance P-like immunoreactivity in the central nervous system of the rat—I. Cell bodies and nerve terminals

Adenosine and the adenine nucleotides have a potent depressant action on cerebral cortical neurons, including identified corticospinal cells Other purine and pyrimidine nucleotides were either weakly depressant (inosine and guanosine derivatives) or largely inactive (xanthine, cytidine, thymidine, uridine derivatives) The 5'-triphosphates and to a lesser extent the 5'-diphosphates of all the purine and pyrimidines tested had excitant actions on cortical neurons Adenosine transport blockers and deaminase inhibitors depressed the firing of cortical neurons and potentiated the depressant actions of adenosine and the adenine nucleotides Methylxanthines (theophylline, caffeine, and isobutylmethylxanthine) antagonized the depressant effects of adenosine and the adenine nucleotides and enhanced the spontaneous firing rate of cerebral cortical neurons Intracellular recordings showed that adenosine 5'-monophosphate hyperpolarizes cerebral cortical neurons and suppresses spontaneous and evoked excitatory postsynaptic potentials in the absence of any pronounced alterations in membrane resistance or of the threshold for action potential generation It is suggested that adenosine depresses spontaneous and evoked activity by inhibiting the release of transmitter from presynaptic nerve terminals Furthermore, the depressant effects of potentiators and excitant effects of antagonists of adenosine on neuronal firing are consistent with the hypothesis that cortical neurons are subject to control by endogenously released purines

Effects of adenosine and adenine nucleotides on synaptic transmission in the cerebral cortex

Adenosine as a putative transmitter in the cerebral cortex. Studies with potentiators and antagonists.

A potent depressant action of adenine derivatives on cerebral cortical neurones.

Microiontophoretically applied adenine nucleotides depressed the firing of corticospinal and other unidentified cerebral cortical neurones. Adenosine 3′,5′-cyclic monophosphate was less potent than...

Depression of Corticospinal Cells by Various Purines and Pyrimidines

1. 1. Stimulation of the nucleus locus coeruleus (LC) inhibits the extracellularly recorded electrical activity of corticospinal and other unidentified neurones in the rat cerebral cortex. 2. 2. With 3–4 pulse trains of stimulation, the inhibitions had mean latencies of 32 ± 1.5 msec and 54 ± 2.3 msec (mean ± S.E.M.) for identified and unidentified neurones, respectively. 3. 3. The duration of LC evoked inhibition was 148 ± 4.6 msec and 148 ± 3.7 msec for the two groups of nerve cells. 4. 4. Iontophoretically applied noradrenaline depressed the spontaneous firing of all LC-inhibited cells on which it was tested. 5. 5. The LC-evoked inhibition was reversibly antagonized by MJ 1999 (Sotalol, a β-adrenergic blocker) and was absent in 6-OHDA-treated animals. 6. 6. Phenylephrine and salbutamol had depressant effects on cerebral cortical neurones. 7. 7. The findings show that the LC projection inhibits cerebral cortical neurones and implicate noradrenaline as the transmitter released by these fibres.

J.W. Phillis

Papers

Effects of adenosine and adenine nucleotides on synaptic transmission in the cerebral cortex

Adenosine as a putative transmitter in the cerebral cortex. Studies with potentiators and antagonists.

A potent depressant action of adenine derivatives on cerebral cortical neurones.

Depression of Corticospinal Cells by Various Purines and Pyrimidines

Activation of a noradrenergic pathway from the brain stem to rat cerebral cortex.