Showing papers by "Francesco E. Pontieri published in 1999"

Drug addiction as a disorder of associative learning. Role of nucleus accumbens shell/extended amygdala dopamine.

Abstract: Conventional reinforcers phasically stimulate dopamine transmission in the nucleus accumbens shell. This property undergoes one-trial habituation consistent with a role of nucleus accumbens shell dopamine in associative learning. Experimental studies with place- and taste-conditioning paradigms confirm this role. Addictive drugs share with conventional reinforcers the property of stimulating dopamine transmission in the nucleus accumbens shell. This response, however, undergoes one-trial habituation in the case of conventional reinforcers but not of drugs. Resistance to habituation allows drugs to repetitively activate dopamine transmission in the shell upon repeated self-administration. This process abnormally facilitates associative learning, leading to the attribution of excessive motivational value to discrete stimuli or contexts predictive of drug availability. Addiction is therefore the expression of the excessive control over behavior acquired by drug-related stimuli as a result of abnormal strenghtening of stimulus-drug contingencies by nondecremental drug-induced stimulation of dopamine transmission in the nucleus accumbens shell.

Reduced dopamine in peripheral blood lymphocytes in Parkinson's disease

Abstract: The early clinical symptoms of Parkinson's disease (PD) may be difficult to perceive and are frequently overlooked. Thus, interest has focused on the identification of biological or instrumental markers that may contribute to the early diagnosis of PD, with the aim of introducing neuroprotective therapies at the very start of illness. Impairment of nigrostriatal dopamine transmission can be visualized in vivo by functional imaging techniques, but these are rather complex and expensive examinations, available only in selected institutions. Here we show that dopamine content and tyrosine hydroxylase immunoreactivity are reduced in peripheral blood lymphocytes (PBL) in the early stages of PD. These data suggest that PBL may represent a simple and useful tool with which to identify precociously dopamine impairment in PD.

Yawning in Parkinson's disease

Abstract: To the Editor: We read with interest the Clinical/Scientific Note by Drs. Goren and Friedman1 on levodopa-induced yawning in PD. They state that “yawning has not been associated with treated or untreated PD,” and they suggest that “if yawning is a dopamine-mediated phenomenon in humans it should be seen in PD patients treated with levodopa and dopamine agonists.”1 Indeed, this is the case. It is well known that apomorphine, a direct D1–D2 dopamine receptor agonist, frequently induces yawning just before the onset of the motor effect, both in experimental animals and in patients with PD.2 Yawning was clearly described since the early clinical trials with apomorphine in the 1950s.3,4 More recently this effect was confirmed in the larger clinical series that have marked the revival of this drug as an adjunct therapy for advanced PD, either as intermittent boluses or as a continuous subcutaneous infusion via portable minipumps.5 Interestingly, the widespread reintroduction of apomorphine in the therapeutic arsenal for PD is due to the observation that pretreatment with the peripheral dopamine receptor blocking agent domperidone could prevent apomorphine-induced nausea, drowsiness, and arterial hypotension, but not yawning.6 …

Effects of haloperidol on the expression of lymphocyte dopamine receptor mRNAs in the rat.

Abstract: 1. 1. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate the effects of haloperidol treatment (1 mg/kg/day for 2, 7 or 21 consecutive days) on the expression of D1B and D3 dopamine receptor mRNAs in the rat lymphocytes. 2. 2. The expression of D1B receptor mRNA was significantly decreased after 2 days of treatment and progressively returned toward basal values at the end of treatment. Conversely, haloperidol failed to modify the expression of lymphocyte D3 receptor mRNA. 3. 3. These results indicate short-lasting dynamic changes of expression of lymphocyte D1B dopamine receptor mRNA by haloperidol and suggest that the effects of dopamine and dopaminergic drugs on the immune system might be mediated, at least in part, by direct interaction of these substances with dopamine receptors on lymphocyte membrane.