Intravenous cocaine self-administration in rats is reduced by dietaryl-tryptophan

Abstract

Rats were trained to self-administer intravenously-delivered cocaine. Four lever-press responses resulted in a cocaine infusion (0.2 mg/kg) during daily 24-h sessions. The rats were also trained to obtain water from tongue-operated solenoid-driven drinking spouts. Ground food and water from a standard drinking bottle were also available. When cocaine injections reached stable levels, L-tryptophan was mixed with the rats' food for 5 days. Three concentrations of L-tryptophan (2, 4, and 8%) were tested in different groups of five rats each. Three other groups of five rats each received the same L-tryptophan treatments; however, in these rats saline was substituted for cocaine and a sweet drinking solution consisting of glucose and saccharin (G + S) replaced water in the automatic drinking device. Two other groups consisting of five rats each self-administered a higher (0.4 mg/kg) or lower (0.1 mg/kg) unit dose of cocaine and food adulterated with 4% tryptophan. At the two higher concentrations L-tryptophan reduced cocaine infusions by at least 50% during the 5 days of treatment, and cocaine infusions returned to baseline levels within 48 h after the regular diet was restored. Responding reinforced by the G + S solution was not altered by any of the L-tryptophan concentrations. Food intake was substantially lowered by the 8% L-tryptophan concentration; however, water intake, responding on an inactive lever, and the number of saline infusions were not affected by addition of L-tryptophan to the food. L-Tryptophan had the same magnitude of effect on self-administration of the 0.1 and 0.2 mg/kg unit doses of cocaine, but behavior maintained by the highest cocaine dose (0.4 mg/kg) was resistant to the effect of L-tryptophan. The results of this experiment indicate that L-tryptophan reduces behavior reinforced by IV cocaine infusions.

Serotonergic Attenuation of the Reinforcing and Neurochemical Effects of Cocaine in Squirrel Monkeys

“…For example, the reinforcing efficacy of cocaine can be enhanced by chemical lesions of brain 5-HT systems (Roberts et al, 1994), whereas dietary supplement with 5-HT precursors can attenuate cocaine self-administration in rodents (Carroll et al, 1990). Furthermore, self-administration of cocaine is decreased by 5-HT uptake inhibitors in rats (Richardson and Roberts, 1991) and monkeys (Kleven and Woolverton, 1993), although similar effects are obtained on food-maintained behavior.…”

Enhanced Locomotor, Reinforcing, and Neurochemical Effects of Cocaine in Serotonin 5-Hydroxytryptamine 2C Receptor Mutant Mice

“…Activation of the mesolimbic DA system, consisting of projections from the midbrain ventral tegmental area (VTA) to forebrain regions, including the nucleus accumbens (NAcc), is considered a critical event underlying the psychostimulant and reinforcing effects of cocaine (Wise, 1984). In general, activation of the serotonergic system appears to inhibit these effects of cocaine, whereas manipulations that decrease serotonergic transmission increase the psychostimulant and reinforcing properties of cocaine (Carroll et al, 1990;Loh and Roberts, 1990;Morrow and Roth, 1996;Herges and Taylor, 1999). Serotonergic neurons in the dorsal raphe project to the VTA and the NAcc (Azmitia and Segal, 1978;Herve et al, 1987;Van Bockstaele et al, 1994;Van Bockstaele et al, 1996) and influence dopaminergic transmission (Herve et al, 1979;Kelland et al, 1993;Prisco and Esposito, 1995;Brodie and Bunney, 1996), suggesting that regulation of mesolimbic dopaminergic activity may play an important role in the serotonergic modulation of cocaine effects.…”

Augmented cocaine-induced accumbal dopamine efflux, motor activity and place preference in rats fed with a tryptophan-deficient diet

“…In fact, treatment with 5-HT agonists reduces self-administration of both cocaine and amphetamine in rats [5,6,28] while a reduction in brain 5-HT content, following destruction of serotonergic neurons by neurotoxic lesions induced by 5,7-dihydroxytryptamine increases self-administration of these psychostimulants in rats [20,21]. Thus, serotonergic tone appears to be strongly implicated in the effect of psychostimulant drugs.…”

“…Indeed, Molina et al [22] found that administration of TRP attenuates cocaine-induced motor activity and DA release in the NAcc of rats. Moreover, Carroll et al [5] reported that acute or chronic TRP treatment reduces intravenous cocaine self-administration in rats. Similarly, amphetamine selfadministration was attenuated in rats fed with TRP supplemented food [28].…”