Non-psychostimulant drugs of abuse and anxiogenic drugs activate with differential selectivity dopamine transmission in the nucleus accumbens and in the medial prefrontal cortex of the rat

Abstract

In rats vertically implanted with concentric dialysis probes in the medial prefrontal cortex and in the medial nucleus accumbens, morphine, ethanol and nicotine failed to modify extracellular dopamine in the medial prefrontal cortex at doses that were fully effective in raising extracellular dopamine in the nucleus accumbens. Conversely, the aversive/anxiogenic drugs picrotoxin, pentylenetetrazol and FG 7142, administered at subconvulsant doses, increased extracellular dopamine in the medial prefrontal cortex but failed to do so in the nucleus accumbens. Systemic administration of low doses of the 5HT3 antagonist ICS 205930, previously reported to prevent the increase of extracellular dopamine in the nucleus accumbens elicited by morphine, nicotine, ethanol and haloperidol (Carboni et al. 1989) as well as by stress (Imperato et al. 1990), also prevented the increase of extracellular dopamine elicited in the prefrontal cortex by anxiogenic drugs. Therefore, mesocortical and mesolimbic dopamine neurons show clear-cut differences in the reactivity to drugs of abuse and to aversive drugs but are both modulated by a facilitatory serotonergic input mediated by 5HT3 receptors.

Co-release of noradrenaline and dopamine in the prefrontal cortex after acute morphine and during morphine withdrawal

“…As expected from previous results (Rossetti et al 1993;Bassareo et al 1996), in the PFC acute morphine administration (5 mg/kg IP) reduced extracellular NA concentration by about 30%, but failed to modify extracellular DA levels ( Fig. 2A).…”

“…Moreover, the lack of effect of acute morphine on extracellular DA is in apparent contrast to the stimulant effect of morphine on VTA neurons (Matthews and German 1984), and on the increased DA output in the nucleus accumbens (Pothos et al 1991;Bassareo et al 1996).…”

“…Conversely, acute morphine activates the firing and bursting activity of dopaminergic neurons in the ventral tegmental area (VTA) (Matthews and German 1984), and increases dopamine (DA) release in the nucleus accumbens (Pothos et al 1991;Bassareo et al 1996).…”

Nicotine addiction: insights from recent animal studies

“…An acute systemic injection of nicotine, such as with other drugs of abuse, increases the extracellular concentrations of DA in the terminal fields of the mesolimbic system (Imperato et al 1986;Maisonneuve and Glick 1999;Mifsud et al 1989;Pontieri et al 1996; for a review see , the nigrostriatal pathway (Di Chiara and Imperato 1988;Toth et al 1992), and the mesocortical pathway (Bassareo et al 1996;Summers and Giacobini 1995;Toth et al 1992). Repeated nicotine injections in rats (0.4 mg/kg nicotine tartrate subcutaneously for 7 days) increased the dopamine release caused by local nicotine administration in the striatum, as measured with in vivo microdialysis (Marshall et al 1997).…”

Haloperidol increases the disruptive effect of alcohol on spatial working memory in rats: a dopaminergic modulation in the medial prefrontal cortex

“…The mesocorticolimbic dopaminergic system, referred to as the brain reward circuit, has suggested a strong role of dopamine (DA) in the effects of addictive drugs, including alcohol. DA has been implicated in rewarding effects, such as the subjective experience of "pleasure" (Brodie et al 1999;Hyman and Malenka 2001), in mechanisms involved in the development of dependence (Bassareo et al 1996;Giacchino and Henriksen 1996;Peters et al 2000), and in reinforcing actions of abused drugs such as alcohol (Weiss and Porrino 2002). In fact, many structures of the brain reward circuit show increases in the turnover of DA after alcohol administration (Tabakoff and Hoffman 1992;Di Chiara 1995;O'Brien et al 1995).…”