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The effects of microinjections of cholinergic agents into the substantia nigra pars compacta on dopamine (DA) efflux in the anterior dorsomedial striatum of urethane-anesthetized rats were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose-dependent augmentation of DA efflux as evidenced by increases in the chronoamperometric signals was observed in the striatum following nigral microinjections of the cholinergic agonists nicotine or carbachol. Enhancing extracellular concentrations of ACh in the substantia nigra by intranigral infusions of the cholinesterase inhibitor neostigmine also resulted in an increase in the chronoamperometric signal corresponding to DA overflow in the striatum. These stimulatory effects of neostigmine on DA efflux in the striatum were confirmed using in vivo microdialysis. Compared to sham-operated control animals, quinolinic acid lesions of the pedunculopontine tegmental nucleus (PPTg) resulted in an attenuation of the stimulatory effects of intranigral neostigmine on DA efflux in the striatum. In contrast, these treatments resulted in an enhancement of striatal DA efflux in response to nigral infusions of the direct ACh receptor agonist nicotine. Combined, these data suggest that PPTg cholinergic neurons are indirectly involved in regulating the activity of the striatum by modulating the activity of DA neurons in the substantia nigra of the rat.

Stearate-modified graphite paste electrodes were implanted chronically into dopamine terminal regions in the nucleus accumbens or caudate nucleus of the rat. Reverse dialysis was used to demonstrate a selective response of these electrodes to dopamine, but not 3,4-dihydroxyphenylacetic acid or ascorbic acid. In a separate behavioural experiment, a significant increase in the chronoamperometric response was observed during presentation of a conditional stimulus predictive of food, and the electrochemical response remained elevated during and following consumption of the meal. Similar trends were observed from electrodes in the caudate nucleus. These data confirm the activation of mesolimbic dopamine neurons by incentive stimuli predictive of food and possibly by consumption of food. Together with other recent data on sex- and thirst-related increases in dopamine levels in the nucleus accumbens, these findings are consistent with a role for the nucleus accumbens as an interface between motivation and activation of the motor system.

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