Palmatier Matthew I, Evans-Martin F Fay, Hoffman Alycia, Caggiula Anthony R, Chaudhri Nadia, Donny Eric C, Liu Xiu, Booth Sherri, Gharib Maysa, Craven Laure, Sved Alan F
Department of Psychology, University of Pittsburgh, 3137 Sennott Square, 210 S. Bouquet St., Pittsburgh, PA 15260, USA.
Psychopharmacology (Berl). 2006 Mar;184(3-4):391-400. doi: 10.1007/s00213-005-0183-4. Epub 2005 Oct 25.
Nicotine has two effects on reinforcement in traditional self-administration paradigms. It serves as a primary reinforcer by increasing the probability of behaviors that result in nicotine delivery. However, nicotine also potently enhances behaviors that result in the delivery of nonpharmacological reinforcers.
The present study sought to dissociate these two effects of nicotine on reinforcement.
For one group of rats (2 lever), a nonpharmacological reinforcer [visual stimulus (VS)] was available for pressing one lever. Nicotine infusions were available for pressing a different lever. A second group (NIC + VS) received more traditional self-administration training; both the VS and nicotine were delivered for pressing a single active lever. Control groups received either nicotine infusions (NIC only) or VS presentations (VS only) for pressing the active lever.
Nicotine alone was a weak reinforcer; the VS alone was slightly more reinforcing than nicotine. When these two reinforcers were combined (NIC + VS), response rates were synergistically increased. For the 2-lever group, responding on the nicotine lever was weak, matching the response rates of rats receiving nicotine alone. However, responding on the VS lever was potently enhanced in this group; equaling the response rates for rats receiving both reinforcers for making a single response (NIC + VS).
These data indicate that the reinforcement-enhancing effects of nicotine are very potent even when only moderate quantities of the drug are self-administered. Moreover, they provide the first demonstration that the reinforcement-enhancing and primary reinforcing effects of nicotine can be dissociated behaviorally.
在传统的自我给药范式中,尼古丁对强化作用有两种影响。它通过增加导致尼古丁递送的行为的概率,充当主要强化物。然而,尼古丁也能有力地增强导致非药物强化物递送的行为。
本研究旨在区分尼古丁对强化作用的这两种影响。
对于一组大鼠(双杠杆),按压一个杠杆可获得非药物强化物[视觉刺激(VS)]。按压另一个不同的杠杆可获得尼古丁输注。第二组(尼古丁+视觉刺激)接受了更传统的自我给药训练;按压单个活动杠杆可同时获得视觉刺激和尼古丁。对照组按压活动杠杆时,分别接受尼古丁输注(仅尼古丁组)或视觉刺激呈现(仅视觉刺激组)。
单独使用尼古丁时强化作用较弱;单独使用视觉刺激时的强化作用略强于尼古丁。当这两种强化物结合(尼古丁+视觉刺激)时,反应率协同增加。对于双杠杆组,大鼠对尼古丁杠杆的反应较弱,与单独接受尼古丁的大鼠的反应率相当。然而,该组大鼠对视觉刺激杠杆的反应显著增强;与接受两种强化物进行单一反应的大鼠的反应率相当(尼古丁+视觉刺激)。
这些数据表明,即使仅自我给药适量的药物,尼古丁的强化增强作用也非常显著。此外,它们首次证明了尼古丁的强化增强作用和主要强化作用在行为上可以区分。