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Biomedical subjects

C J Slawecki

Publications and source records attributed to C J Slawecki.

9 recordsLinked to original sources

Presentation of an ethanol-paired stimulus complex alters response patterns during extinction.

It has been hypothesized that environmental stimuli previously paired with ethanol consumption play a role in excessive ethanol intake. This study examined the ability of orally self-administered ethanol to establish a tone-light stimulus complex as a conditioned reinforcer (CSR). Male Long-Evans rats were trained to orally self-administer 10% ethanol (10E) using the sucrose-substitution procedure. During training, a tone-light stimulus complex was paired with ethanol presentation in a stimulus complex paired (SC-paired) group but not in a control group. Responding during extinction in the presence and absence of the stimulus complex was then examined. Following the initiation of ethanol self-administration, 10E maintained greater responding in the SC-paired group compared to the control group. When the stimulus complex was presented contingent on responding during extinction, the rate of extinction was slightly attenuated in the SC-paired group but not in the control group. The altered rate of extinction in the SC-paired group was characterized by: 1) a slight decrease in total session responding over successive days of extinction and 2) a transient attenuation of extinction burst response rate during the first extinction session. These data suggest the stimulus complex could function as a weak CS(R), but overall its ability to maintain lever pressing was minimal.

Animals

Exposure to sucrose-quinine solutions does not increase ethanol consumption.

The taste of ethanol can be aversive or preferred based on prior experience with ethanol consumption. A preference for ethanol's taste is thought to result from the association of ethanol's taste with its neuropharmacological activity. However, acclimation to ethanol's aversive taste may also play a role in increased ethanol consumption following prolonged exposure. The present study examined if acclimation to a bitter-sweet tastant, which has been suggested to share similar taste qualities with ethanol, would increase ethanol intake with only minimal prior experience of an association of ethanol intake with its neuropharmacological activity. Male Long-Evans rats were trained to drink 10% sucrose during 20-min sessions. The consumption of 0-20% ethanol was then determined before and after exposure to a sucrose-quinine solution. Before the sucrose-quinine taste acclimation procedure, the initial intake of sucrose-quinine was low and similar to 5% ethanol. After the acclimation procedure, increases in sucrose-quinine intake, but not ethanol intake, were observed. These data could indicate that any similarity in the taste qualities of sucrose-quinine and ethanol solutions are diminished following exposure to sucrose-quinine. Alternatively, the differential changes in sucrose-quinine and ethanol intake could be the result of being differentially regulated by a combination of taste and postingestive factors. Overall, these data indicate that exposure to sucrose-quinine, which resulted in increased intake of sucrose-quinine, was not sufficient to alter ethanol intake. Rather, exposure to taste and postingestive factors associated with ethanol may be necessary to increase ethanol intake.

Alcohol Drinking

Appetitive and consummatory behaviors in the control of ethanol consumption: a measure of ethanol seeking behavior.

Models of ethanol self-administration in animals have demonstrated that ethanol can reinforce a variety of behaviors, independent of ethanol's caloric or fluid properties. However, the processes that control self-administration remain unclear. Determining factors related to ethanol seeking behavior, independent of consumption, is central to the concepts of intake regulation. The model described in this article proposes a method to separate the initial appetitive (seeking) behavior from the following consummatory (drinking) behavior to assess each behavior type. Rats were trained to lever press to gain access to a drinking tube connected to a fluid bottle containing either 10% ethanol or 3% sucrose for 20 min. When the response requirement to obtain access to the tube was increased, it was found that both solutions supported the same amount of responding (breakpoint was at approximately a fixed ratio 32 requirement), indicating equal reinforcer strength. However, regardless of the response requirement, if access to the fluids occurred, intakes were not changed. This suggests that factors besides those of reinforcer efficacy are important in controlling the size of the consummatory bout. Based on these findings, we believe that this model will be useful in determining factors related to seeking behaviors and the control of drinking bout size.

Alcohol Drinking

Intranucleus accumbens amphetamine infusions enhance responding maintained by a stimulus complex paired with oral ethanol self-administration.

Six male Long-Evans rats were trained to self-administer 10% ethanol (v/v) during 30 min operant sessions. A licking response on an empty drinking tube resulted in the presentation of reinforcement from an automatic dipper. During the initiation of ethanol self-administration, a tone-light stimulus complex was paired with all ethanol presentations. When 10% ethanol maintained responding, guide cannulae aimed at the nucleus accumbens (NAcc) were implanted into the brain. The ability of the paired stimulus complex to reinforce a new operant response (i.e., a lever press) was then examined. To test for the development of the new response, responding on one lever resulted in presentation of only the paired tone-light stimulus complex (contingency-associated lever) while responding on an alternate lever had no programmed consequences (no contingency-associated lever). Prior to some new response sessions, amphetamine (5-20 microg/microl) was infused into the NAcc to examine the influence of dopamine on responding maintained by the stimulus complex. Ethanol intake during the sessions prior to new response testing averaged 0.49 +/- 0.07 g/g. During new response sessions no significant differences in lever pressure during no-drug conditions (control, sham, injection or vehicle injection) were observed between the contingency-associated and no contingency-associated levers. Intra-NAcc infusion of amphetamine (5-20 microg/microl) resulted in significant increases in lever pressing only on the contingency-associated lever. These data suggest that increasing NAcc dopamine levels with amphetamine enhanced the ability of the stimulus complex to function as a reinforcer. Further studies examining the ability of potentially more salient stimuli (i.e., taste of ethanol) to function as conditioned reinforcers associated with ethanol self-administration are warranted due to the apparent inability of the paired tone-light stimulus complex to function as a reinforcer without amphetamine-induced activation of the NAcc.

Animals

Differential changes in sucrose/ethanol and sucrose maintained responding by independently altering ethanol or sucrose concentration.

Increased reinforcing efficacy of sucrose/ethanol solutions in comparison to sucrose solutions has been previously demonstrated. However, the contribution of the components of the sucrose/ethanol solution is not well defined. The present study used a multiple schedule of reinforcement to evaluate the differential changes in reinforcer presentations as sucrose or ethanol concentrations were altered. Male Long-Evans rats were trained to press a lever on a multiple fixed ratio 4-fixed ratio 4 schedule which was composed of alternating 2-min components. During one component, 5% sucrose/10% ethanol was presented as the reinforcer and, in the second component, 5% sucrose was presented. Independent manipulations of the ethanol concentration (0, 5, and 20%) in the sucrose/ethanol solution or sucrose concentration (0, 10, and 20%) in the sucrose solution were then performed. Increasing the ethanol concentration in the sucrose/ethanol solution resulted in decreases in reinforcer delivery but increases in ethanol intake (grams per kilogram) and total session caloric intake. Increasing the sucrose concentration in the sucrose solution resulted in significant increases in sucrose reinforcer delivery and total session caloric intake. During the concentration manipulations, the number of reinforcers presented of the unchanged reinforcer was not affected. Differential changes in the pattern of reinforcer presentation after ethanol and sucrose concentration manipulations during successive access periods suggest that sucrose and sucrose/ethanol maintained responding are differentially regulated. Changes in sucrose maintained responding after increases in the sucrose concentration were observed early in the session suggesting a strong influence of taste in regulating intake. Changes in sucrose/ethanol maintained responding after increases in the ethanol concentration occurred later in the session and suggest that postingestive effects (i.e., pharmacology) play a major role in the regulation of sucrose/ethanol intake. In addition, the differential patterns of sucrose/ethanol and sucrose maintained behavior suggest that the ethanol component of the sucrose/ethanol solution plays an important role in maintaining sucrose/ethanol reinforced behavior.

Alcohol Drinking

Changes in oral ethanol self-administration patterns resulting from ethanol concentration manipulations.

A variety of initiation procedures have been used to develop oral ethanol consumption. Using the sucrose-substitution procedure, oral self-administration of ethanol-water solutions with ethanol concentrations as high as 40% can be initiated in food- and fluid-sated rats. An important question for these models is the relationship between ethanol concentration and self-administration patterns after initiation. This study examined the differential patterns of ethanol self-administration maintained by a range of ethanol solutions (10 to 30%) over a 5-week period, compared with rats maintained on 10% ethanol for 5 weeks. In 43 male Long Evans rats, the sucrose-substitution procedure was used to initiate responding maintained by 10% ethanol on a Fixed Ratio 4 schedule of reinforcement. The ethanol concentration presented was then increased to 30% in stepwise fashion and then returned to 10% [Ethanol Concentration Manipulation (ECM) group, n = 32], or 10% ethanol was maintained as the reinforcer for 5 weeks [Control (Con) group, n = 11]. Significant increases in ethanol intake and decreases in responding were associated with increased ethanol concentration. Although no overall differences in total session responding were observed in either group between week 1 and week 5 (10E vs. 10E), examination of changes in initial low responders of the ECM group revealed significant increases in responding that were not observed in the initial low responders of the Con group. Significant increases in momentary response rates were observed on both the ECM and Con groups, independent of the ethanol concentration presented. Increases in response rate in the ECM group were the result of increases in initial low rate and high rate responders; however, the increased response rates in the Con group were the result of increases only in the initial low rate responders. These data suggest that the ECM procedure can aid in the initiation of ethanol self-administration and may be particularly useful in rats of heterogeneous stock.

Alcohol Drinking

Effect of amphetamine on behavior maintained by sucrose: interaction of reinforcement schedule and food restriction.

A multiple schedule (Mult FR 10 VI 30") was employed to examine the interaction of reinforcement schedule and food restriction on amphetamine's effects on lever pressing behavior. High response rates were observed in fixed ratio (FR) 10 components. Significantly lower response rates were observed under the variable interval (VI) 30" schedule. In the nonrestricted feeding condition, significant decreases in high rate FR 10 responding occurred after administration of 1.0 mg/kg amphetamine while lower rates under the same schedule were increased by 0.30 and 1.0 mg/kg amphetamine. In contrast, VI 30" responding was minimally effected at any amphetamine dose. Food restriction resulted in significant increases in responding in both schedule components. Under food restriction, significant decreases in responding were observed only in the FR 10 components at the highest amphetamine dose. The data indicate that amphetamine produced rate-convergent effects and the susceptibility of the animal to these effects was dependent on the schedule of reinforcement and food restriction.

Animals

Norepinephrine and serotonin receptors in the paraventricular nucleus interactively modulate ethanol consumption.

The homeostatic function of the hypothalamus has long been recognized. In particular, the role of the paraventricular nucleus (PVN) in regulating ingestive behavior has been of interest. Infusions of serotonin and norepinephrine into the PVN are correlated with nutrient selective decreases and increases in consumatory behavior, respectively. Given the wide range of homeostatic functions of the hypothalamus, it is plausible that similar hypothalamic mechanisms may also be involved in the regulation of ethanol intake. This study examined the effects of PVN infusions of serotonin (5-HT) and norepinephrine (NE) on ethanol intake in a 1-hr limited-access two-bottle paradigm. When intake of 6% (v/v) ethanol versus water stabilized, male Wistar rats were implanted with stainless steel guide cannulae aimed at the PVN. After recovery, NE (20, 50, and 100 nmol), 5-HT (5 and 25 nmol), and their combination (NE 50 nmol + 5-HT 5 nmol) were microinjected into the PVN in a volume of 0.5 microliter/side over 1 min. Baseline ethanol intake was approximately 1.0 g/kg and ethanol preference (milliliters ethanol per total milliliters) was approximately 60%. Both 20 and 50 nmol of NE significantly increased absolute ethanol intake by 50% and relative ethanol intake by approximately 30%. Corresponding decreases were observed in water intake. Neither dose of 5-HT when administered alone altered ethanol or water consumption, but the 5-nmol dose of 5-HT attenuated the increase observed after NE (50 nmol) administration. These data demonstrate that NE and 5-HT receptors in the PVN interact in the modulation of ethanol ingestion. This finding suggests that homeostatic regulatory functions of the hypothalamus are involved in ethanol intake, and a perturbation of this system may influence excessive drinking.

Alcohol Drinking

Dopaminergic and opiate agonists and antagonists differentially decrease multiple schedule responding maintained by sucrose/ethanol and sucrose.

Similar neurobiological mechanisms are hypothesized to influence ethanol- and food-related reinforcement processes. This study examined the ability of compounds with dopaminergic or opiate activity to selectively alter responding maintained by a sucrose/ethanol solution in comparison to a sucrose solution. Long-Evans rats were trained to press a lever using 5% sucrose/10% ethanol and 5% sucrose as the reinforcers on a multiple Fixed Ratio 4 Fixed Ratio 4 schedule of reinforcement. When stable responding was established, the effects of intraperitoneally administered amphetamine (0.0-3.0 mg/kg), haloperidol (0.0-1.0 mg/kg), morphine (0.0-10.0 mg/kg), and naloxone (0.0-10.0 mg/kg) were examined on total session reinforcer presentation and presentation of each reinforcer within individual multiple schedule components. Prior to drug treatment, the total number of reinforcer presentations of the sucrose/ethanol solution was significantly greater than sucrose reinforcer presentations, suggesting the sucrose/ethanol solution was a more efficacious reinforcer. All agents administered decreased responding maintained by sucrose/ethanol and sucrose. The dose-effect curves for sucrose/ethanol were shifted to the left compared to sucrose, suggesting that although the compounds did not selectively impact sucrose/ethanol-maintained responding, sucrose/ethanol-maintained responding was more sensitive to the effects of these compounds.

Amphetamine