Nicotine does not improve discrimination of brain stimulation reward by rats

Abstract

Rats were trained to shuttle between two selected ("ON") arms of a Y maze, to obtain electrical stimulation of the medial forebrain bundle. Each shuttle response was rewarded with a brief pulse train. Repetitive entries into the same "ON" arm were not rewarded, nor were entries made into the third ("OFF") arm. Every 67s, stimulation was made available from a different pair of arms. Test sessions lasted for 80 min, beginning immediately after SC injection. Undrugged subjects responded faster, and with a greater proportion of rewarded responses, the higher the stimulation current. In non-tolerant rats, nicotine (0-0.4 mg/kg) depressed responding and induced ataxia shortly after injection; from 40 min, nicotine increased low rates of responding but decreased high rates. All these effects were dose-dependent. Mecamylamine (2.0 mg/kg) prevented the initial depressant action. With repeated daily injections of nicotine (0.4 mg/kg), a marked stimulant action emerged which replaced the initial depressant action, and this was dose-dependent. However, responding was increased by nicotine even when brain stimulation was not available ("time-out"). In contrast, an additional "rate-free" index based on discrimination showed that nicotine did not augment the rewarding properties of the brain stimulation.

Differential effects of cholinergic drugs on discriminative cues and self-stimulation produced by electrical stimulation of the ventral tegmental area

“…Together, these results suggested that muscarinic receptor activation inhibits ICSS, whereas nicotinic receptor activation both faciiitates and inhibits VTA ICSS in a dose-dependent manner. This conc!usion is consistent with previously reported effects of cholinergic drugs on both VTA and LH ICSS (O!ds and Domino I969 ;Newman 1972;Clarke and Kumar 1983;Schaefer and Michael i986).…”

Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement

“…Initial evidence came from studies of brain stimulation reward, where both amphetamine (Stein and Ray 1960;Stein 1961) and cocaine (Crow 1970) lowered thresholds for brain self-stimulation reward in rats. A comparable impact of nicotine on brain stimulation reward has also been demonstrated (Ivanova and Greenshaw 1997;Bozarth et al 1998a;Bozarth et al 1998b; but see also Clarke and Kumar 1983). In particular, nicotine was shown to induce parallel leftward shifts in rate-frequency functions for both lateral hypothalamic and midline mesencephalic brain stimulation, which could reflect a synergism between nicotine and the reinforcing properties of brain stimulation (Bauco and Wise 1994).…”

Mecamylamine Attenuates Cue-Induced Reinstatement of Nicotine-Seeking Behavior in Rats

“…For example, we have shown that rats readily selfadminister a b2-selective nicotinic receptor agonist (Liu et al, 2003). Conversely, nicotinic receptor antagonists have been found to block nicotine's effects on striatal dopamine release and turnover (Haikala and Ahtee, 1988;Nisell et al, 1994), nicotine-induced dopaminergic signaling and neuronal excitation (Hamada et al, 2004;Yin and French, 2000), the locomotor effects of nicotine (Clarke and Kumar, 1983;Curzon et al, 1996;Kuo et al, 1999), and nicotine-induced hypothermia (Haikala and Ahtee, 1988;Zarrindast et al, 2001). Similarly, nicotinic antagonists precipitate nicotine withdrawal (Adams and Cicero, 1998;Hildebrand et al, 1999;Watkins et al, 2000b) and decrease rates of nicotine self-administration (Corrigall and Coen, 1989;Donny et al, 1999;Shoaib et al, 1997;Watkins et al, 1999).…”