title: Blockade of beta-adrenergic receptors prevents amphetamine-induced behavioural sensitization in rats: a putative role of the bed nucleus of the stria terminalis.
abstract: Recent findings have given evidence a role for noradrenergic transmission in the mechanisms underlying behavioural sensitization to psychostimulants. This work was undertaken to investigate the possible role of beta-adrenergic receptors in amphetamine-induced behavioural sensitization in rats. Rats were sensitized by a single administration of amphetamine (1 mg/kg s.c.) and challenged with the same dose 7 d later. The beta(1) /beta(2) -adrenergic receptor antagonists timolol (10 mg/kg i.p.) and nadolol (10 mg/kg i.p.), which respectively cross or do not readily cross the blood-brain barrier, were injected prior to the first or second amphetamine administration. Timolol, but not nadolol, prevented the initiation of behavioural sensitization without interfering with the expression of the sensitized response or the acute locomotor response to amphetamine. Since we found amphetamine-induced fos-activated cells closely associated with dopamine beta-hydroxylase immunoreactive varicosities in the bed nucleus of the stria terminalis (BNST), we investigated the effect of a bilateral micro-injection of timolol into this nucleus. Similarly to systemic administration, intra-BNST timolol (2.5 microg/side) prevented the development of behavioural sensitization. These results suggest that central beta-adrenergic receptors could specifically modulate early neuronal changes leading to the development of behavioural sensitization to psychostimulants, and that the BNST could be an important part of the brain circuitry involved in these long-term neuroadaptations.
authors.affiliation: Laboratoire de Neuropharmacologie et Neurochimie, INSERM U512, Université Claude Bernard Lyon 1, Faculté de Pharmacie, 8 Avenue Rockefeller, 69373 Lyon, France.
authors.forename: Joyce
authors.initials: J
authors.lastname: Colussi-Mas
authors.forename: Fany
authors.initials: F
authors.lastname: Panayi
authors.forename: Hélène
authors.initials: H
authors.lastname: Scarna
authors.forename: Bernard
authors.initials: B
authors.lastname: Renaud
authors.forename: Anne
authors.initials: A
authors.lastname: Bérod
authors.forename: Laura
authors.initials: L
authors.lastname: Lambás-Señas
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000661:Amphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D016762:Genes, fos / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009248:Nadolol / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000502:physiology*; D013999:Timolol / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D000697:Central Nervous System Stimulants; D009248:Nadolol; D013999:Timolol; D000661:Amphetamine; D004299:Dopamine beta-Hydroxylase