Biomedical subjects

A Bechara

Publications and source records attributed to A Bechara.

At least 37 records · Page 2Linked to original sources

PubMed1997

Deciding advantageously before knowing the advantageous strategy.

Deciding advantageously in a complex situation is thought to require overt reasoning on declarative knowledge, namely, on facts pertaining to premises, options for action, and outcomes of actions that embody the pertinent previous experience. An alternative possibility was investigated: that overt reasoning is preceded by a nonconscious biasing step that uses neural systems other than those that support declarative knowledge. Normal participants and patients with prefrontal damage and decision-making defects performed a gambling task in which behavioral, psychophysiological, and self-account measures were obtained in parallel. Normals began to choose advantageously before they realized which strategy worked best, whereas prefrontal patients continued to choose disadvantageously even after they knew the correct strategy. Moreover, normals began to generate anticipatory skin conductance responses (SCRs) whenever they pondered a choice that turned out to be risky, before they knew explicitly that it was a risky choice, whereas patients never developed anticipatory SCRs, although some eventually realized which choices were risky. The results suggest that, in normal individuals, nonconscious biases guide behavior before conscious knowledge does. Without the help of such biases, overt knowledge may be insufficient to ensure advantageous behavior.

Aged↗

PubMed1997

Neurobiological constraints on behavioral models of motivation.

The application of neurobiological tools to behavioral questions has produced a number of working models of the mechanisms mediating the rewarding and aversive properties of stimuli. The authors review and compare three models that differ in the nature and number of the processes identified. The dopamine hypothesis, a single system model, posits that the neurotransmitter dopamine plays a fundamental role in mediating the rewarding properties of all classes of stimuli. In contrast, both nondeprived/deprived and saliency attribution models claim that separate systems make independent contributions to reward. The former identifies the psychological boundary defined by the two systems as being between states of nondeprivation (e.g. food sated) and deprivation (e.g. hunger). The latter identifies a boundary between liking and wanting systems. Neurobiological dissociations provide tests of and explanatory power for behavioral theories of goal-directed behavior.

Animals↗

PubMed1997

Comparative study of papaverine plus phentolamine versus prostaglandin E1 in erectile dysfunction.

PURPOSE: We compared the efficacy and short-term adverse effects of 1 ml. 30 mg./ml. papaverine plus 0.5 mg./ml. phentolamine versus 1 ml. 30 micrograms./ml. prostaglandin E1 in patients undergoing pharmacological erection testing. MATERIALS AND METHODS: A total of 60 patients (mean age 58 years) with a history of sexual erectile dysfunction longer than 6 months was randomly classified into 6 groups to be tested 1 week apart with the 2 solutions and with placebo to evaluate erection response and short-term adverse effects. RESULTS: Of the patients tested with papaverine plus phentolamine 54% responded with erections adequate for penetration, compared to 50% of those tested with prostaglandin E1 (p > 0.05). Prolonged erection occurred in 18% of patients tested with papaverine plus phentolamine and 15% of those tested with prostaglandin E1 (p > 0.05). Pain was reported by 15 and 35% of patients, respectively (p < 0.05). CONCLUSIONS: One ml. 30 mg./ml. papaverine plus 0.5 mg./ml. phentolamine has the same efficacy and equal prolonged erection rate as 1 ml. 30 micrograms./ml. prostaglandin E1 but the latter agent induces significantly more pain.

Adult↗

PubMed1996

Lesions of the lateral parabrachial nucleus block the aversive motivational effects of both morphine and morphine withdrawal but spare morphine's discriminative properties.

This study examined if the aversive properties of morphine, the aversive properties of morphine withdrawal, and the discriminative properties of morphine are mediated by common neurobiological substrates. Lesions of the lateral parabrachial nucleus, which blocked the aversive properties of morphine in the conditioned taste aversion paradigm, also blocked the acquisition of conditioned place aversions to environments paired with the aversive properties of morphine withdrawal in morphine-dependent rats. When morphine and saline were used as cues in a discrimination task, however, both sham-operated and lesioned rats were able to solve the task.

Animals↗

PubMed1996

Prostaglandin E1 versus mixture of prostaglandin E1, papaverine and phentolamine in nonresponders to high papaverine plus phentolamine doses.

PURPOSE: We evaluated the efficacy of 40 micrograms/ml, prostaglandin E1 versus a combination of 17.64 mg./ml. papaverine hydrochloride, 0.58 mg./ml. phentolamine mesylate and 5.8 micrograms/ml. prostaglandin E1 (3-drug mixture). MATERIALS AND METHODS: A total of 32 patients randomly received 1 ml. of either medication by the intracavernous route. All patients had presented with erectile dysfunction longer than 6 months in duration and had failed to respond to high doses of papaverine (60 mg.) plus phentolamine (1 mg). RESULTS: Of 32 patients 7 (22%) responded to prostaglandin E1 and 16 (50%) to the 3-drug mixture, achieving erections allowing penetration (grade E4 or E5, p < 0.05). Pain was reported by 41% of the patients receiving prostaglandin E1 and 12.5% administered the 3-drug mixture. CONCLUSIONS: The 3-drug mixture may be regarded as more effective than prostaglandin E1 alone in inducing an erectile response with a decreased incidence of pain.

Adult↗

PubMed1995

Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans.

A patient with selective bilateral damage to the amygdala did not acquire conditioned autonomic responses to visual or auditory stimuli but did acquire the declarative facts about which visual or auditory stimuli were paired with the unconditioned stimulus. By contrast, a patient with selective bilateral damage to the hippocampus failed to acquire the facts but did acquire the conditioning. Finally, a patient with bilateral damage to both amygdala and hippocampal formation acquired neither the conditioning nor the facts. These findings demonstrate a double dissociation of conditioning and declarative knowledge relative to the human amygdala and hippocampus.

Acoustic Stimulation↗

PubMed1995

Neurobiology of withdrawal motivation: evidence for two separate aversive effects produced in morphine-naive versus morphine-dependent rats by both naloxone and spontaneous withdrawal.

In drug-naive rats, the rewarding effects of morphine are blocked by lesions of the tegmental pedunculopontine nucleus (TPP), but not by neuroleptics. In dependent rats (chronically treated with morphine), morphine reward is blocked by neuroleptics, but not by TPP lesions. Just as this activation of opiate receptors in naive versus dependent rats produces different mechanisms of reward, this study concludes that reduced opioid activity on these opiate receptors produces different mechanisms of aversion. Neuroleptics blocked the conditioned place aversions produced by naloxone and spontaneous withdrawal in morphine dependent, but not naive, rats, without attenuating the somatic withdrawal syndrome induced by naloxone in dependent rats. The researchers suggest that the aversive effects of endogenous opioid withdrawal in naive rats are mediated by different neural substrates than the aversive effects of exogenous opioid withdrawal in dependent rats.

Animals↗

PubMed1994

Acquisition of conditional discriminations in hippocampal lesioned and decorticated rats: evidence for learning that is separate from both simple classical conditioning and configural learning.

This study examined whether hippocampal or neocortical lesions would impair acquisition of a discrimination task using taste aversions. Rats were injected with a drug 15 min before a flavored solution-lithium chloride pairing. On alternate days, vehicle injections preceded and followed access to the same flavored solution. Rats learned to consume significantly more of the flavored solution after vehicle injections than after drug injections. Rats with hippocampal lesions or neonatal decortication performed as well as controls. Rats with hippocampal lesions also learned a similar task in which visual and textural cues predicted whether access to a flavored solution would be followed by an injection of lithium chloride or vehicle. However, these hippocampal lesions did impair performance in the Morris water task. Occasion setting may involve a type of learning dissociated from both simple classical conditioning and configural learning.

Animals↗

PubMed1994

Neuroleptics block high- but not low-dose heroin place preferences: further evidence for a two-system model of motivation.

The researchers studied whether 2 separate motivational systems in the brain underlie the rewarding effects of morphine. The brainstem tegmental pedunculopontine nucleus (TPP) is involved in mediating the motivational effects of opiates in nondeprived (drug-naive) rats, whereas dopamine transmission is necessary in mediating the motivational effects of opiates in deprived rats (opiate withdrawal). The results show that heroin's motivational properties obey the same boundary between a nondeprived and a deprived motivational state. Bilateral ibotenic acid lesions of the TPP blocked the acquisition of a place preference for an environment paired with 0.05 mg/kg heroin (a dose that induces no withdrawal aversion) but had no effect on place preference for an environment paired with 0.5 mg/kg heroin (a dose that does induce withdrawal aversion). Dopamine antagonist pretreatment produced the opposite pattern of results.

Animals↗

PubMed1993

The parabrachial nucleus: a brain stem substrate critical for mediating the aversive motivational effects of morphine.

Bilateral ibotenic acid lesions of the lateral, but not the medial, parabrachial nucleus (PBN) blocked conditioned taste aversion (CTA) induced by morphine but not conditioned place preference induced by morphine. The same lateral PBN lesions also blocked conditioned place aversion produced by low intraperitoneal doses of morphine (shown to produce aversion, instead of preference, due to a restricted action on gut opiate receptors). Lateral PBN lesions did not block CTA produced by LiCl. Cerebral peduncle lesions that destroyed the direct descending projections from the visceral cortex to the PBN did not block CTA induced by morphine, nor did ibotenic acid lesions of the tegmental pedunculopontine nuclei (shown to block place preference produced by even high morphine doses). It is suggested that the lateral PBN is a critical link in the neural pathway carrying the aversive motivational effects of opiates from the gut into the central nervous system, independent of the neural pathway carrying the rewarding motivational effects of morphine.

Animals↗

PubMed1992

Lesions of the tegmental pedunculopontine nucleus: effects on the locomotor activity induced by morphine and amphetamine.

One of the important questions in the neurobiology of motivation asks how the incentive impact of stimuli acting on the limbic system of the forebrain are ultimately translated into action and approach behavior. Bilateral ibotenic acid lesions of the tegmental pedunculopontine nucleus (TPP) (a brainstem output of the limbic system that receives neuronal input from limbic forebrain and midbrain sites identified as primary sites for psychoactive drug reward) have been shown previously to block the acquisition, but not the retention, of morphine and amphetamine conditioned place preferences in formerly drug-naive rats. These results suggest a deficit in the processing of the unconditioned rewarding effects of these drugs. The TPP projects to widespread parts of the brain and spinal cord involved in various somatomotor responses. Thus, we investigated the role of the TPP in morphine- and amphetamine-induced locomotion as assessed in an open field. We report that TPP lesions blocked the locomotor excitation, as well as the conditioned hyperactivity, produced by amphetamine. TPP lesions also blocked the conditioned increase in locomotion, but not the catalepsy, produced by morphine. TPP lesions were behaviorally specific in that the analgesic properties of morphine in a tail-flick test were not attenuated, nor did the lesions affect the locomotion induced by naloxone-precipitated withdrawal in morphine-dependent animals. We suggest that the neural circuits mediating the acute rewarding effects of drug stimuli acting at forebrain sites exit the limbic system in the TPP region of the brainstem, where motivation gains access to (or is isomorphic with) motor systems that initiate approach and exploration.

Amphetamine↗

PubMed1992

A single brain stem substrate mediates the motivational effects of both opiates and food in nondeprived rats but not in deprived rats.

Drug-naive and morphine-dependent rats both preferred places paired with morphine over unfamiliar neutral places. Morphine-dependent, but not naive, rats avoided places paired with the lack of morphine (i.e., withdrawal). Food-sated and food-deprived rats both preferred places paired with food over unfamiliar neutral places. Food-deprived, but not sated, rats avoided places paired with the lack of food (i.e., hunger). Lesions of the tegmental pedunculopontine nucleus (TPP) blocked the morphine- and food-conditioned place preferences in drug-naive and food-sated rats, respectively. TPP lesions failed to block morphine- and food-conditioned place preferences as well as morphine withdrawal-conditioned and hunger-conditioned place aversions in morphine-dependent and food-deprived rats, respectively. These results suggest that separate neural mechanisms subserve deprivation- and non-deprivation-induced motivation.

Animals↗

PubMed1992

Chronic exposure to morphine does not alter the neural tissues subserving its acute rewarding properties: apparent tolerance is overshadowing.

Drug-naive, but not morphine-dependent, rats preferred places paired with morphine (2 mg/kg) over unfamiliar neutral places. Both drug-naive and morphine-dependent rats preferred places paired with higher doses of morphine (20 mg/kg) over unfamiliar places. Lesions of the tegmental pedunculopontine nucleus (TPP) blocked the conditioned place preferences produced by both 2 and 20 mg/kg morphine in drug-naive rats but not the preferences produced by 20 mg/kg morphine in dependent rats. When morphine-dependent animals received withdrawal-alleviating doses of morphine (20 mg/kg) 3.5 hr before pairing one environment with 2 mg/kg morphine, they showed morphine-conditioned place preferences that were abolished by TPP lesions. The apparent behavioral tolerance to the TPP-mediated rewarding effects may have resulted from overshadowing by separate withdrawal-related motivational mechanisms.

Animals↗

PubMed1992

Neurobiology of motivation: double dissociation of two motivational mechanisms mediating opiate reward in drug-naive versus drug-dependent animals.

Separate brain manipulations double dissociate two motivational mechanisms underlying the rewarding effects of opiates. Lesions of the brain stem tegmental pedunculopontine nucleus block the rewarding properties of morphine in drug-naive, but not in drug-dependent, rats. Neuroleptics (which block the action of the neurotransmitter dopamine) abolished opiate motivational effects in drug-dependent, but not in drug-naive, rats in place conditioning paradigms. This second dopaminergic opiate reward mechanism mediates morphine's alleviation of the withdrawal distress associated with abstinence in opiate-dependent animals. Furthermore, neuroleptic-induced blockade of food-related motivational effects in food-deprived, but not in food-sated (non-food-deprived), animals suggests that the neural substrates of motivational events do not dissociate along the line between different rewarding stimuli but along the line between deprivation and nondeprivation.

Animals↗

PubMed1992

[Test with vasoactive drugs: its predictive value in the diagnosis of erectile sexual dysfunction of venous origin].

The practicability and sensitivity of the test with vasoactive drugs, the first method performed in our flow studies, make it an invaluable method for orienting the diagnosis. Our findings show that in 65% of the patients with a partial response to the drug-induced erectile test, dysfunction may arise from pure or associated venous leakage, which must be confirmed by dynamic cavernosometry and/or cavernosography.

Adult↗

PubMed1989

[Is it useful to ask questions to assess the strength of urination flow?].

In order to determine the value of the interview conducted to assess the micturitional stream of our patients, we compared in 200 cases what the patients said about their micturition against their maximum flow rate (QMx). We demonstrated that 79% of those who said they voided with a "bad stream" had QMx less than or equal to 10 ml/sec. Only 65% of those who said they voided with a "good stream" had a QMx less than or equal to 15 ml/sec. Of those with QMx less than or equal to 10 ml/sec. (73 patients), only 15% had reported a "bad stream". Thus, we believe it is not reliable and of little interest to ask our patients about the strength of their micturitional stream. It would only be useful in those who reported a "bad voiding". To our knowledge, this is the first study that documents the discrepancy between data from the interview and the maximum flow rate.

Adolescent↗

PubMed1989

The tegmental pedunculopontine nucleus: a brain-stem output of the limbic system critical for the conditioned place preferences produced by morphine and amphetamine.

The potent reinforcing properties of psychoactive drugs have been attributed to the activation of motivational processes localized to the limbic system. We investigated the role of 2 specific outputs of the forebrain limbic system, the tegmental pedunculopontine nucleus (TPP) and the periacqueductal gray (PAG) of the pons-midbrain, in the positive motivational effects of morphine and amphetamine. We now report that the TPP, but not the PAG nor other nearby regions, is a critical site in the neural system subserving the rewarding effects of both opiates and stimulants. Bilateral ibotenic acid lesions of the TPP blocked the positive reinforcing effects of both morphine and amphetamine in naive rats as measured in a conditioned place preference paradigm. However, TPP lesioned animals were still capable of acquiring a conditioned place preference to an environment paired with the peripheral opiate antagonist methylnaltrexone. This suggested that TPP lesions did not cause nonspecific deficits in the basic learning mechanisms underlying conditioned place preferences. Furthermore, while the TPP was critical for the acquisition of a conditioned preference to an environment paired with morphine in naive rats, rats that had acquired a morphine conditioned place preference prior to the lesions were capable of retaining and demonstrating these place preferences after lesions of the TPP. This again demonstrates that TPP lesions are producing an unconditioned deficit in motivation rather than a deficit in learning or memory. Finally, direct comparisons of the place preference data of individual animals with their correspondent TPP lesion sites indicated that the most effective lesions overlapped to a greater degree TPP perikarya with descending, rather than ascending, axons. This suggests that motivational information generated by drug stimuli acting at "upstream" neural structures flows in a descending direction through the TPP region of the brain stem. These results suggest that opiates and stimulants must ultimately activate a single brain-stem substrate in order to have a positive motivational impact. It is hypothesized that the neural circuits mediating the rewarding effects of drug stimuli acting at forebrain sites exit the limbic system in the TPP region of the brain stem, where motivation may ultimately influence or be isomorphic with the elicitation of motor responses subserving approach and exploration.

Amphetamine↗

PubMed1988

Morphine preexposure attenuates the aversive properties of opiates without preexposure to the aversive properties.

Evidence that action on peripheral opiate receptors is necessary to produce aversive effects with morphine, enabled us to determine whether preexposure to these aversive effects is necessary for the later attenuation of morphine's aversive properties. We found that blockade of the aversive effects of morphine with the peripheral antagonist methylnaltrexone during morphine preexposure had no effect on the later attenuated development of conditioned taste aversions to morphine. Moreover, in the same rat morphine preexposure did not affect the development of a place preference to an environment paired with injections of morphine. The results suggest that an effect of central opiate action is able to attenuate the later peripheral aversive, but not the central rewarding, effects of morphine.

Animals↗