Amphetamine-induced activation of forebrain EEG is prevented by noradrenergic β-receptor blockade in the halothane-anesthetized rat

• Published in: Psychopharmacologia Vol. 148; no. 3; pp. 307 - 313
• Main Authors: BERRIDGE, C. W, MORRIS, M. F
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.02.2000
• Subjects: Amphetamine - pharmacology; Anesthesia; Animals; Biological and medical sciences; Electroencephalography - drug effects; Halothane - pharmacology; Male; Medical sciences; Neuropharmacology; Norepinephrine - physiology; Pharmacology. Drug treatments; Prosencephalon - drug effects; Prosencephalon - physiology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta - physiology; Timolol - pharmacology; Amphetamine derivatives; Intravenous administration; Rat; CNS stimulant; Psychotropic; Rodentia; Central nervous system; Electrophysiology; Dose activity relation; β-Adrenergic receptor; Vertebrata; Mammalia; Animal; Arousal; Intracerebral administration; Amfetamine; Antagonist; Mechanism of action; Adrenergic pathway; Brain (vertebrata)
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130050055

Amphetamine (AMPH)-like stimulants represent an intensively studied class of psychoactive drugs. Despite the well-known and potent arousal-enhancing effects of these drugs, the neurobiological substrates of AMPH-induced arousal have rarely been examined explicitly. Activity of the locus coeruleus-noradrenergic system is causally and positively related to behavioral and electroencephalographic (EEG) indices of arousal. For example, activation of locus coeruleus neurons or stimulation of medial basal forebrain noradrenergic beta-receptors elicits activation of forebrain EEG in the anesthetized rat. Further, stimulation of noradrenergic beta-receptors within the medial basal forebrain elicits a substantial increase in alert, active waking. These and other observations suggest that at least some of the arousal-enhancing actions of AMPH-like stimulants derive from AMPH-induced increases in noradrenergic neurotransmission at beta-receptors. The current study examines the extent to which AMPH-induced activation of cortical EEG is dependent on actions of central beta-receptors. The effects of intracerebroventricular (ICV; 2 microl) pretreatment with either vehicle (artificial extracellular fluid) or the beta-antagonist, timolol (25, 50 or 100 microg), on the cortical EEG activating effects of intravenous AMPH (0.15 mg/kg) were examined in the halothane-anesthetized rat. EEG was recorded on polygraph and video recording tape and later analyzed using power spectral analyses (PSA). AMPH-induced alteration in cortical EEG activity was measured using PSA in vehicle- and timolol-pretreated animals. Neither vehicle nor timolol ICV infusions altered cortical EEG activity patterns. In vehicle-pretreated animals, AMPH elicited a robust activation of cortical EEG, characterized by the substantial decrease in large-amplitude, slow-wave activity. Timolol pretreatment dose-dependently prevented AMPH-induced cortical EEG activation. This effect of timolol was statistically significant at the 50 microg and 100 microg dose. These observations indicate that, under these experimental conditions, AMPH-induced activation of the forebrain is dependent on actions of noradrenergic beta-receptors. Combined with previous observations, these observations support the hypothesis that AMPH-induced increases in arousal involve noradrenergic neurotransmission at beta-receptors.