title: Norepinephrine and brain damage: alpha noradrenergic pharmacology alters functional recovery after cortical trauma.
abstract: The goal of these experiments was to evaluate the effects of some drugs affecting noradrenergic (NE) synaptic transmission, commonly prescribed following stroke or traumatic brain injury, on functional recovery. Measurement of recovery from a transient hemiplegia produced by a traumatic unilateral focal contusion in sensorimotor cortex (SMCX) of rats was used to assess the effects of chronic haloperidol (HAL) treatment begun early (1 day) or late (18 days to recovered animals) after injury. Additionally, using the same model, the effects of a single administration of drugs with selective action at NE receptors were also evaluated early or late (30 days) after injury. These drugs were: phenoxybenzamine (PBZ), an alpha 1-NE antagonist; prazosin (PRAZ), an alpha 1-NE antagonist; yohimbine (YOH), an alpha 2-NE antagonist; propranolol (PROP), a beta 1- and 2-NE receptor antagonist; methoxymine (METHOX), an alpha 1-NE agonist; and clonidine (CLON), an alpha 2-NE agonist. The data indicate that drugs with antagonistic effects at alpha 1 NE receptors, including HAL and PRAZ but not PROP, administered early after SMCX contusion retard locomotor recovery. Beneficial effects of enhancing NE transmission by METHOX or YOH were not observed. In animals recovered from beam walk (BW) deficits, a single administration of PBZ or PRAZ (alpha 1 NE antagonists) or CLON (alpha 2 NE agonist) transiently reinstated hemiplegic symptoms. The nonspecific beta NE receptor antagonist PROP had no effect in recovered animals. A single dose of HAL had no effect in recovered animals, but a BW deficit transiently developed in some animals following chronic treatment. The data are discussed with reference to drug contraindications noted in clinical studies of recovery from poststroke aphasia and cognition in demented patients with degenerative brain disease.
authors.affiliation: Department of Psychology, University of New Mexico, Albuquerque 87131.
authors.forename: D M
authors.initials: DM
authors.lastname: Feeney
authors.forename: V S
authors.initials: VS
authors.lastname: Westerberg
mesh_terms: D000818:Animals; D001925:Brain Damage, Chronic / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013003:Somatosensory Cortex / Q000187:drug effects*; D013565:Sympatholytics / Q000494:pharmacology*; D013566:Sympathomimetics / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D011941:Receptors, Adrenergic; D013565:Sympatholytics; D013566:Sympathomimetics; D009638:Norepinephrine