The alpha4beta2 agonist SIB 1765F, but not the alpha7 agonist AR-R 17779, cross-sensitises to the psychostimulant effects of nicotine.
BACKGROUND
Repeated administration of nicotine leads to an augmentation of its locomotor activating effects. Although studies have begun to identify the nicotinic receptor subtype(s) mediating the psychostimulant properties of nicotine, none as yet have investigated the subtypes which contribute to the process of sensitisation.


OBJECTIVE
We therefore investigated cross-sensitisation to nicotine using subjects chronically treated with two nicotine subtype-selective agonists in an attempt to identify the relative contribution of each to the sensitisation process.


METHODS
Rats received ten daily injections of either vehicle, nicotine (0.4 mg/kg), the alpha7-agonist AR-R 17779 (20 mg/kg), or the alpha4beta2-agonist SIB 1765F (3 mg/kg), and their subsequent locomotor response to acute challenge with each of these compounds was assessed.


RESULTS
Chronic administration of both nicotine and SIB 1765F, but not AR-R 17779, resulted in an enhanced locomotor response to acute challenge with either nicotine or SIB 1765F but not AR-R 17779.


CONCLUSIONS
These data support a role for the alpha4beta2 receptor in both the initiation and expression of sensitisation to the psychomotor stimulant effects of nicotine.
Grottick
A J
AJ
Pharma Division, F. Hoffman-La Roche AG, Basel, Switzerland. andrew_john.grottick@roche.com
Wyler
R
R
Higgins
G A
GA
D000818:Animals; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D013141:Spiro Compounds / Q000494:pharmacology*
C408128:AR-R 17779; D001952:Bridged-Ring Compounds; D018722:Nicotinic Agonists; D011725:Pyridines; D011759:Pyrrolidines; D011978:Receptors, Nicotinic; D013141:Spiro Compounds; D009538:Nicotine; C100989:altinicline maleate