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A Bechara

Publications and source records attributed to A Bechara.

48 records · Page 3Linked to original sources
PubMed1988

The dopamine innervation of the visceral cortex mediates the aversive effects of opiates.

We have previously reported that opiates acting on peripheral receptors produce aversive effects whereas opiates acting on central brain receptors produce rewarding effects. The neurotransmitter dopamine (DA) has previously been implicated in both opiate reinforcing (positive) and aversive (negative) effects. We, therefore, chose to investigate the effects of disruption of DA systems on these two motivational properties of the opiate, morphine. Moreover, we sought to determine the brain site where dopamine might act as a mediator of these motivational effects. One group of rats received 6-hydroxydopamine (6-OHDA) lesions of the visceral (agranular insular) cortex to destroy dopaminergic innervation to this area. A separate group of animals were pretreated with intraperitoneal (IP) injections of the DA receptor blocker, alpha-flupenthixol (0.8 mg/kg), followed in both groups by 15 mg/kg (IP) morphine. Both 6-OHDA-lesioned and alpha-flupenthixol-pretreated subjects failed to develop the normal aversion to saccharin seen in control groups following conditioned taste aversion training with morphine. In a place conditioning paradigm, the aversive effects produced by low IP injections of morphine (acting on peripheral receptors) were blocked by 6-OHDA lesions of the visceral cortex. However, DA depletion of the visceral cortex did not disrupt the ability of animals to acquire a morphine place preference. Taken together, these results indicate that DA innervation of the visceral cortex mediates the aversive, but not the rewarding, properties of opiates.

Animals↗
PubMed1987

Peripheral receptors mediate the aversive conditioning effects of morphine in the rat.

Previous evidence has shown that morphine produces positive reinforcing effects (as measured in the place conditioning paradigm) through an action in the central nervous system (CNS). The aversive conditioning effects of morphine (as measured in the place and taste conditioning paradigms) were produced when drug action was restricted to peripheral sites, particularly in the gut region. We now demonstrate that most of the aversive conditioning effects of morphine (using place and taste conditioning paradigms) are receptor mediated effects exerted through an action on peripheral opiate receptors. The conditioned taste aversions induced by intraperitoneal (IP) morphine (15 mg/kg) but not amphetamine (1 mg/kg) were attenuated by low IP doses of opiate antagonists (0.1 mg/kg of naltrexone or 1 mg/kg of the peripherally acting antagonist methynaltrexone (MN]. Morphine-, but not amphetamine-induced conditioned taste aversions were also attenuated in animals whose small sensory neurons, bearing the majority of primary afferent opiate receptors, were destroyed by neonatal treatments with capsaicin. In the place conditioning paradigm, the aversive conditioning effects produced by low IP administrations of morphine were blocked by opiate antagonists. Intraperitoneal pretreatments with 1 mg/kg of the quaternary opiate antagonist MN (which does not cross the blood-brain barrier effectively) were shown to block the conditioned place aversions produced by low IP doses of morphine (0.05 mg/kg), but not the place aversions produced by lithium chloride (75 mg/kg IP), or by high doses of naloxone (10 mg/kg SC). These results demonstrate that the aversive conditioning effects of morphine are primarily mediated through an action on peripheral opiate receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1987

Kappa receptors mediate the peripheral aversive effects of opiates.

Previous evidence has suggested that endogenous and exogenous opioids produce positive reinforcing effects through an action on central nervous system opiate receptors and aversive effects through an action on peripheral opiate receptors. In order to investigate the pharmacological specificity of the opiate aversive effects to peripheral opiate receptor subtypes, drug naive rats were administered various subcutaneous or intraperitoneal dose of the specific kappa receptor agonist U50,488 (0.005-16 mg/kg) and run in a place conditioning paradigm. The results were compared to previously published data on the motivational effects of morphine, collected using identical experimental procedures. Regardless of the route of administration, the majority of doses of U50,488 produced conditioned place aversions, whereas increasing doses of morphine produced conditioned place preferences. Only a low dose of morphine (0.05 mg/kg intraperitoneally but not subcutaneously) was shown to produce significant place aversions, suggesting a local gut effect. Vagotomy blocked the aversive properties of morphine, and in the present report shifted the motivational effects of moderate doses of U50,488 into preferences. U50,488 produced aversions at a dose that was 5 times lower than the low dose of morphine that produced aversive effects. Even at very high doses, U50,488 did not produce the conditioned place preferences seen with morphine. These high dose aversions induced by U50,488 were attenuated by a low intraperitoneal dose of the kappa antagonist Mr2266. In order to investigate the possible actions of peripheral, endogenous kappa agonists, a dose-response curve was generated in the place conditioning paradigm from separate groups of naive rats injected with various intraperitoneal doses of the specific kappa antagonist Mr2266 (0.001-10 mg/kg) or its inactive isomer Mr2267 (0.01-10 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMedDate not supplied

Insensitivity to future consequences following damage to human prefrontal cortex.

Following damage to the ventromedial prefrontal cortex, humans develop a defect in real-life decision-making, which contrasts with otherwise normal intellectual functions. Currently, there is no neuropsychological probe to detect in the laboratory, and the cognitive and neural mechanisms responsible for this defect have resisted explanation. Here, using a novel task which simulates real-life decision-making in the way it factors uncertainty of premises and outcomes, as well as reward and punishment, we find that prefrontal patients, unlike controls, are oblivious to the future consequences of their actions, and seem to be guided by immediate prospects only. This finding offers, for the first time, the possibility of detecting these patients' elusive impairment in the laboratory, measuring it, and investigating its possible causes.

Adult↗
PubMedDate not supplied

Opposite motivational effects of endogenous opioids in brain and periphery.

Many psychoactive drugs, including the opiates, have been shown to have paradoxical reinforcing effects. Opiates produce positive reinforcing effects when they are paired with visual and textural environmental stimuli in rats, yet, at similar doses and over the same routes of administration, produce aversive effects, as shown when they are paired with taste stimuli. Similarly, in human, the positive reinforcing effects of opiates are well known to addicts and recreational drug users, yet patients receiving opiates as analgesics often report nauseous reactions. At present there is no evidence to differentiate between the neural substrates that mediate these opposite motivational effects. We now report an initial step in the resolution of this paradox by demonstrating that endogenous and exogenous opioids produce positive reinforcing effects through an action on brain opiate receptors, and aversive effects through an action on peripheral opiate receptors (especially in the gut).

Animals↗
PubMedDate not supplied

Clitoral hemodynamic changes after a topical application of alprostadil.

We performed duplex ultrasonography of the clitoris to assess the local hemodynamic changes after a topical application of alprostadil. Color duplex ultrasonography was used to evaluate 18 women before and after the application of 1 g of 0.2% alprostadil gel. The peak systolic velocity and end diastolic velocity showed a statistically significant difference after the application. All women showed labial and clitoral engorgement, 72% reported a pleasant sensation of warmth, and no systemic side effects were found. These findings are similar to the values reported after sexual stimulation, indicating that topical vasoactive drugs might help in the differential diagnosis of the vascular component of female sexual dysfunction.

Administration, Topical↗
PubMedDate not supplied

Failure to respond autonomically to anticipated future outcomes following damage to prefrontal cortex.

Following damage to specific sectors of the prefrontal cortex, humans develop a defect in real-life decision making, in spite of otherwise normal intellectual performance. The patients so affected may even realize the consequences of their actions but fail to act accordingly, thus appearing oblivious to the future. The neural basis of this defect has resisted explanation. Here we identify a physiological correlate for the defect and discuss its possible significance. We measured the skin conductance responses (SCRs) of 7 patients with prefrontal damage, and 12 normal controls, during the performance of a novel task, a card game that simulates real-life decision making in the way it factors uncertainty, rewards, and penalties. Both patients and controls generated SCRs after selecting cards that were followed by penalties or by reward. However, after a number of trials, controls also began to generate SCRs prior to their selection of a card, while they pondered from which deck to choose, but no patients showed such anticipatory SCRs. The absence of anticipatory SCRs in patients with prefrontal damage is a correlate of their insensitivity to future outcomes. It is compatible with the idea that these patients fail to activate biasing signals that would serve as value markers in the distinction between choices with good or bad future outcomes; that these signals also participate in the enhancement of attention and working memory relative to representations pertinent to the decision process; and that the signals hail from the bioregulatory machinery that sustains somatic homeostasis and can be expressed in emotion and feeling.

Adult↗
PubMedDate not supplied

[Flow studies in patients with sexual erectile dysfunction. Review of the physiology and the adopted method].

Further insight into the physiology of erection acquired in recent years had led to the development of new methods that have enhanced the evaluation of erectile dysfunction. These new methods will permit a more precise diagnosis and, consequently, the management of this condition can be based on scientific and not empirical methods. To date, many questions remain unanswered and many points have not been elucidated. Using a precise methodology will permit us to corroborate or correct what has been done up until now and to develop new methods of investigation. The present study briefly reviews the physiology of erection and describes a method we routinely use.

Adult↗
PubMedDate not supplied

[Brain mechanisms involved in decision-making].

AIM: To review the studies on brain mechanisms in decision making within the framework of the somatic marker hypothesis, and based on experiments employing the Iowa Gambling Task. DEVELOPMENT: An overview of the somatic marker hypothesis is presented together with the review of the main results obtained from research in brain damaged patients, and normal subjects with functional neuroimaging studies, that have led to the identification of the neural structures involved in decision making in humans. CONCLUSIONS: The main region involved in decision making is the ventromedial prefrontal cortex, that integrates sensory, mnesic and emotional information relevant to the task. Other structures intervening in the various relevant processes in decision making are the amygdala (processing and encoding of the emotional signal and its association with contextual stimuli) and the cingulate cortex (process monitoring and response inhibition, especially in situations of uncertainty). The prefrontal dorsolateral cortex would also be involved through the necessary activation of the working memory in the decision making process, especially in the case of complex tasks.

Brain↗