Biomedical subjects

Jason M Uslaner

Publications and source records attributed to Jason M Uslaner.

5 recordsLinked to original sources

PubMed2006

The attribution of incentive salience to a stimulus that signals an intravenous injection of cocaine.

A central premise of a number of theories of addiction is that discrete environmental stimuli repeatedly paired with drugs of abuse acquire incentive salience as a result of Pavlovian learning. There is, however, no unequivocal evidence supporting this assumption. Thus, we employed a Pavlovian conditioning procedure known to imbue non-drug reinforcers with incentive salience and extended it to study the effects of intravenous cocaine. Specifically, we examined whether a cue paired with intravenous cocaine administration would come to elicit approach towards it (sign-tracking), even if no behavioral response were required to receive the cue or drug. We found that when a cue was paired with intravenous cocaine delivery (but not when it was unpaired) rats came to approach and investigate the cue, and did so with increasing rapidity. We conclude that Pavlovian learning can imbue drug-paired cues with incentive salience, making them attractive and "wanted" stimuli. Delineating the neurobiological mechanisms responsible for this process will be important for understanding and treating drug addiction.

Analysis of Variance↗

PubMed2006

Subthalamic nucleus lesions increase impulsive action and decrease impulsive choice - mediation by enhanced incentive motivation?

The subthalamic nucleus (STN) is traditionally thought of as part of a system involved in motor control but recent evidence suggests that it may also play a role in other psychological processes. Here we examined the effects of STN lesions on two measures of impulsivity and found that STN lesions increased 'impulsive action' (produced behavioral disinhibition), as measured by performance on a differential reinforcement of low rates of responding task, but decreased 'impulsive choice' (impulsive decision making), as measured by a delay discounting task. In addition, amphetamine and food restriction increased 'impulsive action' and decreased 'impulsive choice' to a greater extent in STN-lesioned animals than in sham controls. We speculate that these apparently discrepant effects may be because STN lesions enhance the incentive salience assigned to rewards. These findings suggest that the STN may serve as a novel target for the treatment of psychological disorders characterized by deficits in behavioral control, such as drug addiction and attention deficit hyperactivity disorder.

Amphetamine↗

PubMed2005

Subthalamic nucleus lesions enhance the psychomotor-activating, incentive motivational, and neurobiological effects of cocaine.

The subthalamic nucleus (STN) is traditionally thought to be involved in motor control, and dysfunction of the STN is thought to contribute to movement disorders. Here, we show that the STN also plays an important role in motivational processes and the response to drugs of abuse. Specifically, bilateral STN lesions produced a dose-dependent increase in the psychomotor-activating effects of cocaine, the rate at which animals acquired cocaine self-administration, and the motivation for cocaine assessed using a progressive ratio schedule. Furthermore, bilateral STN lesions enhanced the ability of cocaine to induce gene expression in the nucleus accumbens and caudate-putamen, two structures known to be involved in mediating the psychomotor-activating and incentive motivational effects of drugs of abuse. These findings suggest that engagement of the STN serves to dampen the psychomotor-activating and incentive motivational effects of drugs of abuse. Thus, the STN may serve as a novel target for therapeutic interventions aimed at treating drug dependence.

Animals↗

PubMed2003

Cocaine-induced psychomotor activity is associated with its ability to induce c-fos mRNA expression in the subthalamic nucleus: effects of dose and repeated treatment.

Factors that modulate the psychomotor activating effects of amphetamine and cocaine, such as environmental novelty and dose, also regulate the ability of these drugs to induce c-fos mRNA expression in the subthalamic nucleus (STN). We hypothesized therefore that engagement of the STN may be important for stimulant-induced psychomotor activation. To further test this hypothesis we examined whether repeated treatment with cocaine, which enhances its psychomotor activating effects (i.e. produces behavioural sensitization), also enhances its ability to induce c-fos expression in the STN. In addition, given that STN activity is thought to be influenced by preproenkephalin mRNA-containing (ENK+) neurons in the caudate-putamen, we also examined whether repeated cocaine treatment alters c-fos expression in ENK+ cells. We report that: (i) cocaine pretreatment enhances the ability of a cocaine challenge to induce c-fos mRNA expression in the STN, and this effect is most robust at challenge doses where behavioural sensitization is observed; (ii) the ability of cocaine to induce c-fos in the STN is independent of the ability of cocaine to engage ENK+ cells. These results support the idea that the STN is involved in stimulant-induced psychomotor activation and sensitization, but suggest that stimulant-induced engagement of the STN is not dependent on ENK+ cells in the caudate-putamen. These findings may have implications concerning the neurobiological mechanisms underlying the behavioural effects of psychostimulant drugs.

Animals↗

PubMed2003

Amphetamine-induced c-fos mRNA expression in the caudate-putamen and subthalamic nucleus: interactions between dose, environment, and neuronal phenotype.

When administered in a novel environment relatively low doses of amphetamine induce c-fos mRNA in the subthalamic nucleus (STN) and in preproenkephalin mRNA-containing (ENK+) neurons in the caudate-putamen (CPu). When administered at home, however, low doses of amphetamine do not produce these effects. Environmental novelty also facilitates the behavioral effects of acute and repeated amphetamine, but this is dose-dependent. The purpose of the present experiment therefore was to determine if the effect of context on amphetamine-induced c-fos expression is also dose-dependent. It was found that: (i) No dose of amphetamine tested (1-10 mg/kg) induced c-fos in many ENK+ cells when given at home. (ii) When given in a novel environment low to moderate doses of amphetamine (1-5 mg/kg) induced c-fos in substantial numbers of ENK+ cells, but the highest dose examined (10 mg/kg) did not. (iii) Environmental novelty enhanced the ability of low to moderate doses of amphetamine to induce c-fos in the STN, but the highest dose of amphetamine induced robust c-fos mRNA expression in the STN regardless of context. The results do not support the idea that engaging ENK+ cells, at least as indicated by c-fos mRNA expression, is critical to produce robust behavioral sensitization, but do suggest a possible role for the STN. Furthermore, the results highlight the importance of drug-environment interactions on the neurobiological effects of drugs, and have implications for thinking about the circuits by which context modulates the acute and long-lasting consequences of amphetamine treatment.

Amphetamine↗