Behavioral and Electrophysiological Effects of Intracranially Applied Neuropeptides with Special Attention to DC Slow Potential Changesa

Abstract

INTRODUCTIONlntracranial administration of certain neuropeptides can induce massive changes in EEG activity and the DC slow potential, referred to as "spreading depression." Spreading depression, which is difficult to recognize in EEG recordings, has various behavioral consequences. This report summarizes studies dealing with the elicitation of "spreading depression" by neuropeptides and the concomitant behavioral changes commonly (mistakenly) attributed to physiological effects of intracranially injected neuropeptides.The application of various neuropeptides into the brain can elicit behaviors such as "wet-dog'' shaking, grooming, circling, changes in locomotor activity, immobility, analgesia, and barrel rotations. Similar behaviors accompany spreading depression (SD) triggered by electrical, mechanical, or chemical stimulation in certain brain regions. Therefore, we hypothesized that certain behavioral changes that follow the intracranial administration of some neuropeptides are a direct consequence of SD.Our first experiments demonstrated that the injection of certain neuropeptides into the brain can induce SD in the anesthetized animal. The application of nanogram amounts of vasopressin and microgram amounts of ACTHI-,,. Leu-and Metenkephalin, and the Met-enkephalin analogue [~-Ala-2]Met-enkephalinamide (DAME) into the cortex and/or hippocampus of rats elicited SD.1-3 In the case of the enkephalins and DAME, their SD-and seizure-inducing activity was blocked or partly antagonized by the opiate antagonist naloxone.The finding that some neuropeptides are able to induce SD in the anesthetized rat led us to record EEG, DC slow potentials, and behavioral responses concurrently after hippocampal injection of ACTHI-,, and DAME in the freely moving animaL4 We wished to determine whether certain behavioral effects of intracranial injection of neuropeptides (e.g., wet-dog shaking, hyperactivity or immobility, and analgesia for DAME; grooming for ACTHI-,,) are the behavioral expression of SD rather than peptide-specific responses.Comprehensive reviews have been devoted to the phenomenon of SD, including its mechanisms, application, behavioral effects, and methods of The electrophysiological manifestation of SD was probably first described by Leilo in 19U6 as a decrease of spontaneous and evoked EEG activity in the cortex of rabbits after local electrical stimulation. The depression of EEG activity spreads slowly with a velocity of 2-3 mm per min through the brain tissue, e.g., neocortex, nucleus caudatus, hippocampus, and thalamus. Concomitant recording of the DC slow potentials reveals a DC slow potential change (DC-SPC) of up to 40 mV negativity for 1-2 min, followed by a lower but longer-lasting positivity. This sequence constitutes a "wave" of SD. During SD unit activity is depressed, since the neurons are depolarized. Increased neural activity often precedes and/or follows the onset of a wave of SD.Three criteria that have been employed to verify the presence of SD are (1) the negative DC-SPC; (2) the depression of...

Accelerated Hippocampal Spreading Depression and Enhanced Locomotory Activity in Mice with Astrocyte-Directed Inactivation of Connexin43

“…Accelerated SD and enhanced locomotory activity might represent a mild form of the behavioral and electrophysiological responses observed after intrahippocampal injection of KCl in rats (Oitzl and Huston, 1984), possibly related to a generally increased neuronal excitation by activity-related increases in extracellular potassium and glutamate concentrations. The decrease in grooming, untypical for SD-related behavior (Huston and Holzhäuer 1988), points to further effects of the astrocyte-directed Cx43 inactivation specifically counteracting an increase in grooming. For example, changes in oscillatory patterns of Cx43-deficient astrocyte assemblies (Bloomstrand et al, 1999) might affect neuronal oscillation patterns, which are proposed to be related to exploratory and adaptive behavior as well as memory consolidation (Buzsaki 1989;Buzsaki and Chrobak, 1995).…”