Nicotinicdopaminergic Interactions

The brain is an organ of communication. No receptor system acts in isolation from others in providing the functional output of the brain. Nicotinic receptor stimulation induces the release of a variety of neurotransmitters including dopamine (DA). Interactions between nicotinic and DA receptor systems are important for nicotinic

Ventral Hippocampal Nicotinic Antagonist Infusion: B-Arm Maze Accuracy

Mecamylamine

Mecamylamine

O 1 3.3 lO Mecamylamine |g/side

MLA |g/side

FIGURE 7.2 Mecamylamine, MLA, and DH0E effects when infused into the ventral hippocampus (entries to repeat meanĀ±sem).

O 1 3.3 lO Mecamylamine |g/side

MLA |g/side

FIGURE 7.2 Mecamylamine, MLA, and DH0E effects when infused into the ventral hippocampus (entries to repeat meanĀ±sem).

involvement with cognitive function. Nicotinic receptors are heavily concentrated on midbrain dopaminergic nuclei. Nicotine administration promotes DA efflux in the striatum and nucleus accumbens,50 and increases DA concentration in the cortex.62 Conversely, Dj antagonist treatment inhibits ACh release, and Dj agonist treatment enhances ACh release. Curiously, both stimulation and blockade of D2 receptors have been found to reduce ACh release.21 Nicotine-induced DA release has been thought to be important for nicotine dependence. Nicotinic-DA interactions have also been found to be important for cognitive function. Mecamylamine-induced memory deficits are potentiated by D2 antagonist cotreatment and are reversed by D2 agonist cotreatment.4153 Infusion of nicotinic antagonist mecamylamine into the midbrain DA nuclei significantly impairs working memory performance in the radialarm maze.34 Other studies have shown that nicotine disrupts latent inhibition learning, an effect that can be blocked by pretreatment with the DA antagonist haloperi-dol.27 Studies in the laboratory have also shown that the memory-enhancing effects of both acute and chronic nicotine44 interact with DA systems. Chronic (5 mg/kg/day) nicotine increased the memory impairment caused by the Dj agonist dihydrexidine and decreased the improvement caused by the Dj antagonist SCH 23390.30 These findings suggest that nicotinic functions are important in some cognitive disorders traditionally believed to involve primarily DA mechanisms, including attention def-icit/hyperactivity disorder and schizophrenia.

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