| First Author | Collins AC | Year | 1994 |
| Journal | J Pharmacol Exp Ther | Volume | 271 |
| Issue | 1 | Pages | 125-33 |
| PubMed ID | 7965705 | Mgi Jnum | J:29990 |
| Mgi Id | MGI:77512 | Citation | Collins AC, et al. (1994) Sensitivity to nicotine and brain nicotinic receptors are altered by chronic nicotine and mecamylamine infusion. J Pharmacol Exp Ther 271(1):125-33 |
| abstractText | DBA/2 mice were chronically infused with saline (control), 4 mg/kg/hr of nicotine, 4 mg/kg/hr of mecamylamine or nicotine + mecamylamine for 7 days. The binding of L-[H- 3]nicotine was significantly increased in seven of eight brain regions dissected from mice 5 hr after cessation of drug treatment. Similarly, [H-3]nicotine binding was increased in six of eight regions by chronic mecamylamine treatment. Treatment with both drugs led to increases in [H-3]nicotine binding that were at least the sum of the those observed with either drug alone. These increases were partially reversed 48 hr after cessation of treatment. No significant effects of nicotine or mecamylamine treatment on alpha-[I-125]bungarotoxin binding were observed 5 hr after treatment was stopped when assayed using a single ligand concentration. However, saturation analyses of the cerebral cortex detected small increases from control after treatment with nicotine or both drugs. No effects of chronic treatment on alpha-[I- 125]bungarotoxin binding were evident 48 hr after treatment was stopped. Mice treated with nicotine, mecamylamine or both drugs tested 5 hr after withdrawal were less sensitive to acute injection with nicotine than were saline-infused mice. However, the effects of mecamylamine may have been influenced by continued presence of this drug at the time of testing. Mice tested 48 hr after cessation of treatment were more sensitive to nicotine than those tested after 5 hr, but some tolerance to the effects of nicotine persisted in the nicotine- treated mice. The results indicate that either chronic nicotine (agonist) or mecamylamine (antagonist) treatment results in increases in nicotinic receptors measured by high affinity [H-3]nicotine binding, and that the increases observed when both drugs are administered are even greater. Mice treated with nicotine were tolerant to the effects of nicotine both 5 and 48 hr after withdrawal. However, the ability of chronic mecamylamine treatment to induce tolerance to nicotine, or block tolerance induced by chronic nicotine, remains unclear. |
