PT  - JOURNAL ARTICLE
AU  - Candice Drouin
AU  - Laurent Darracq
AU  - Fabrice Trovero
AU  - Gérard Blanc
AU  - Jacques Glowinski
AU  - Susanna Cotecchia
AU  - Jean-Pol Tassin
TI  - α1b-Adrenergic Receptors Control Locomotor and Rewarding Effects of Psychostimulants and Opiates
AID  - 10.1523/JNEUROSCI.22-07-02873.2002
DP  - 2002 Apr 01
TA  - The Journal of Neuroscience
PG  - 2873--2884
VI  - 22
IP  - 7
4099  - http://www.jneurosci.org/content/22/7/2873.short
4100  - http://www.jneurosci.org/content/22/7/2873.full
SO  - J. Neurosci.2002 Apr 01; 22
AB  - Drugs of abuse, such as psychostimulants and opiates, are generally considered as exerting their locomotor and rewarding effects through an increased dopaminergic transmission in the nucleus accumbens. Noradrenergic transmission may also be implicated because most psychostimulants increase norepinephrine (NE) release, and numerous studies have indicated interactions between noradrenergic and dopaminergic neurons through α1-adrenergic receptors. However, analysis of the effects of psychostimulants after either destruction of noradrenergic neurons or pharmacological blockade of α1-adrenergic receptors led to conflicting results. Here we show that the locomotor hyperactivities induced by d-amphetamine (1–3 mg/kg), cocaine (5–20 mg/kg), or morphine (5–10 mg/kg) in mice lacking the α1b subtype of adrenergic receptors were dramatically decreased when compared with wild-type littermates. Moreover, behavioral sensitizations induced by d-amphetamine (1–2 mg/kg), cocaine (5–15 mg/kg), or morphine (7.5 mg/kg) were also decreased in knock-out mice when compared with wild-type. Ruling out a neurological deficit in knock-out mice, both strains reacted similarly to novelty, to intraperitoneal saline, or to the administration of scopolamine (1 mg/kg), an anti-muscarinic agent. Finally, rewarding properties could not be observed in knock-out mice in an oral preference test (cocaine and morphine) and conditioned place preference (morphine) paradigm.Because catecholamine tissue levels, autoradiography of D1 and D2 dopaminergic receptors, and of dopamine reuptake sites and locomotor response to a D1 agonist showed that basal dopaminergic transmission was similar in knock-out and wild-type mice, our data indicate a critical role of α1b-adrenergic receptors and noradrenergic transmission in the vulnerability to addiction.