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H H Samson

Publications and source records attributed to H H Samson.

At least 19 recordsLinked to original sources

Alcohol self-administration: role of mesolimbic dopamine.

It appears clear that ethanol reinforcement, like that of many abused drugs, utilizes the mesolimbic DA pathways. From the data presented on microinjection of DA agonists and antagonists, it would seem that only part of the regulatory process controlling ethanol drinking is directly involved with this pathway. Once drinking has begun, the DA antagonist raclopride results in a rapid termination of drinking. This appears to be a blocking effect of what may be conditioned reinforcement resulting from prior ethanol reinforcement initiation procedures. Microinjection of the DA agonists d-amphetamine and quinpirole prolonged drinking, with little signs of normal termination apparent in the 30-min session in many animals. This appeared to be the result of interference with normal termination processes. While it remains to be demonstrated that oral ethanol consumption results in the release of DA in the nucleus accumbens, evidence from prior work and the present studies support a role for the mesolimbic DA system in ethanol reinforcement.

Alcoholism

Paradoxical effects of nitrous oxide on human memory.

Using the method of adjusted learning, subjects learned number-noun pairs while breathing either placebo or 30% nitrous oxide. Subjects breathing nitrous oxide required more acquisition trials to attain a learning criterion than did subjects breathing placebo. Two weeks later, half of the subjects from each group were administered either placebo or nitrous oxide and were asked to recall the noun that had accompanied each number cue. Results showed that: 1) nitrous oxide inhalation can decrease the accessibility of to-be-recalled material and 2) nitrous oxide administered during the acquisition of material can paradoxically improved the recall of that material 2 weeks later. The additional number of acquisition trials subjects received during nitrous oxide inhalation could potentially account for this paradoxical enhancement of delayed recall; however, correlational analyses suggest this was not the case. No evidence for any state-dependent effects of nitrous oxide on cued recall were found.

Adolescent

Microinjections of dopamine agonists in the nucleus accumbens increase ethanol-reinforced responding.

Long-Evans rats (N = 3) were trained to lever press on a fixed-ratio 4 (FR 4) schedule with ethanol (10% v/v) presented as the reinforcer. Each rat received a total of six bilateral nucleus accumbens microinjections, one per week. They were tested with one physiological saline control, three 20.0-microgram/brain d-amphetamine, and two 6.0-microgram/brain quinpirole injections given 10 min prior to operant sessions. Ethanol-reinforced responding terminated after approximately 10 min during control sessions. Microinjections of the D2 agonist quinpirole and the nonspecific dopamine (DA) agonist d-amphetamine increased total responding but produced slowed response rates that continued for 45-60 min. The slowed response rate produced by d-amphetamine resulted in a peak increase in interresponse times (IRTs) between 8-10 s, whereas quinpirole increased IRTs in the 14- to 16-s range, indicating that nonspecific DA activation resulted in higher rates of ethanol-reinforced responding than specific D2 activation although both drugs decreased local response rates. These data indicate that the amount and temporal extent of ethanol-reinforced responding are increased by microinjections of DA agonists in the nucleus accumbens and support the hypothesis that DA activity in this region is involved in the regulation of ethanol-reinforced responding.

Animals

Neurobiology of alcohol abuse.

Excessive consumption of beverage alcohol (ethanol) is a major health concern worldwide. Understanding the mechanisms by which ethanol affects neural functioning, after both acute and chronic exposure, has become a major goal in the study of alcoholism. With such an understanding, we should be able to institute more effective treatments and preventative measures for alcohol abuse problems. Recent studies have found, contrary to earlier assumptions, that ethanol has selective, dose-dependent effects on various neurotransmitter systems within the CNS. These effects are observed at all levels of analysis, from molecular to behavioral. This review by Herman Samson and Adron Harris covers these recent findings, with the intent of generating questions that will focus further research efforts.

Alcoholism

Alcohol self-administration in a nonrestricted access situation with alcohol-preferring (P) rats.

Genetic variables have been implicated as contributing factors in the development of alcoholic behavior. Rats bred selectively for alcohol preference have been used in laboratory studies to investigate the role of such variables. In the present study, rats from the alcohol preferring (P) line were placed in operant chambers in which food pellets, water, and 10% ethanol (v/v) were available continuously for 23 hr/day. Food pellets (45 mg) were presented on an FR 1 schedule of reinforcement, while ethanol was presented in a 0.1 ml dipper on an FR 4 schedule of reinforcement. Water was available in a drinking tube with licks monitored by a drinkometer. Data were analyzed in terms of both total daily intakes and computer defined bouts. The P rats showed greater daily ethanol intakes compared with Long-Evans (LE) animals previously studied under similar access conditions. The major difference in intake was a result of the P rats having a greater number of daily ethanol drinking bouts, while having only a slight increase in individual bout size. These data indicate that genetic selection for ethanol preference may result in the regulation of ethanol intake by means of changes in the frequency of ethanol drinking bouts but not by changes in bout size.

Alcohol Drinking

Effects of morphine and naloxone on ethanol- and sucrose-reinforced responding in nondeprived rats.

In the following series of experiments, effects of morphine (0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg) and naloxone (0.1, 0.3, and 1.0 mg/kg) were assessed in nondeprived rats trained to leverpress with 10% ethanol, sweetened ethanol, or 5% sucrose and water as the reinforcers. Morphine, at doses of 0.1, 0.3, and 1.0 mg/kg had little effect on responding with ethanol or sweetened ethanol available on a fixed ratio 4 (FR4) schedule of reinforcement, but at the 3.0 mg/kg dose, morphine suppressed responding to near zero. Similar results were obtained when 10% ethanol and water were available on a concurrent FR4 FR4 schedule of reinforcement. When 5% sucrose and water were available concurrently, morphine suppressed responding at 3.0 and 10 mg/kg. Naloxone (0.1, 0.3, and 1.0 mg/kg) decreased responding for ethanol, sweetened ethanol, and sucrose solutions in a dose-dependent manner. Naloxone decreased total number of responses/session by shortening the duration of responding without affecting momentary rate. Overall, the data suggest that the endogenous opioid system plays a role in the ability of ethanol to reinforce operant behavior. However, this role does not appear to be specific to ethanol because similar results were observed with sucrose reinforcement. Failure to find enhanced ethanol intakes following morphine injections in the operant situation suggests that the method used to measure ethanol self-administration makes a difference in assessing the effects of drugs on ethanol intake.

Alcohol Drinking

Response to diazepam in sons of alcoholics.

Alcohol exerts several of its actions via the chloride channel associated with the central GABA-benzodiazepine receptor complex. To explore a possible role for this receptor complex in risk for alcoholism, and to determine whether risk for alcoholism is associated with risk for benzodiazepine abuse, the authors administered intravenous diazepam to 18 sons of male alcoholics (SOAs) and 18 control subjects. Four logarithmically increasing doses of diazepam and matched volumes of placebo were given in randomized order on separate days about 1 week apart. SOAs were significantly more likely than controls to report euphoric responses to diazepam. At some diazepam doses, SOAs were more likely to report feeling "high" and "intoxicated." SOAs and controls did not differ in feeling "drugged." SOAs and controls may differ in expectations regarding the subjective effects of drugs and/or in the function of the central GABA-benzodiazepine receptor complex. These findings also add further evidence for increased pleasurable effects, and thus possibly increased risk for benzodiazepine abuse, in a subgroup of SOAs.

Adolescent

The influence of early postweaning ethanol exposure on oral self-administration behavior in the rat.

The effects of three early ethanol home cage consumption procedures on the maintenance of operant lever responding reinforced by ethanol presentation were examined in the rat. Two groups of rats, 25 and 31 days of age, were exposed to 10% (v/v) ethanol as the only fluid in the home cage for 3 or 10 days. A third group, 31 days of age, were exposed to 10% ethanol or tap water for 24 h, with the fluid alternating daily for 18 days. All animals were subsequently trained to lever press using 10% ethanol reinforcement under a decreasing water restriction schedule. All three groups were found to have substantial ethanol consumption levels during the initial exposure in the home cage, ranging from 11.2 to 11.9 g/kg/day. The animals were all successfully trained to lever press in the operant chamber with ethanol as the reinforcer when limited to 15 ml/day of water in the home cage. The average number of reinforcements per day ranged from 29 to 43.5, yielding ethanol intakes from 1.06 to 1.97 g/kg in the 30-minute operant session. However, when 50 ml/day of water was available in the home cage, ethanol reinforcements were substantially reduced, with intakes which ranged from 0.14 to 0.18 g/kg/day. The data suggest that early exposure does not enhance ethanol's reinforcing properties later in the animal's life. These results were discussed in terms the effect of early ethanol exposure on later ethanol consumption and the role of ethanol initiation procedures in oral self-administration.

Alcohol Drinking

Effects of d-amphetamine injected into the nucleus accumbens on ethanol reinforced behavior.

Rats, initiated to self-administer 10% (v/v) ethanol in an operant situation using the sucrose-fading procedure, received bilateral n. accumbens microinjections of d-amphetamine prior to operant sessions. Doses of 4 micrograms, 10 micrograms and 20 micrograms/brain were administered and some animals also received a 4 microgram/brain dose of LY171555. Three different effects were observed: increased, decreased and no change in total session responding. There was no clear relation between injection area in the n. accumbens and type of effect observed. For either an increase or decrease in total session responding, momentary response rates were decreased. Both d-amphetamine and LY171555 produced similar results. The data support the hypothesis that dopamine in the n. accumbens is involved with ethanol reinforced operant responding but in a complex manner.

Amphetamine

The effects of ethanol initiation procedures on ethanol reinforced behavior in the alcohol-preferring rat.

Rats from the alcohol preferring (P) line developed at Indiana University were initiated to self-administer ethanol orally without food or water restriction using either a sucrose-fading or a secondary-conditioning procedure. Following initiation, they were tested under a variety of operant conditions to examine the ability of ethanol to reinforce lever pressing behavior. Regardless of initiation procedure, the animals maintained lever pressing behavior with ethanol reinforcement, even at ethanol concentrations as high as 40% (v/v). Slightly higher daily session intakes (g/kg) were found at the higher ethanol concentrations following the secondary-conditioning initiation procedure compared with the sucrose-fading technique. When both ethanol and water were concurrently available, the rats showed a high preference for ethanol reinforcement. When varying concentrations of sucrose were substituted for water, the amount of ethanol ingested decreased as the concentration of the alternative sucrose increased. However, if the response requirement for the sucrose was substantially greater than that for ethanol, the rats shifted their responding to the lever associated with ethanol presentation. The results are discussed in relation to prior work using similar procedures with Long-Evans non-selected rats and with the alcohol non-preferring (NP) rat line.

Alcohol Drinking

Reduction in oral ethanol self-administration in the rat by the 5-HT uptake blocker fluoxetine.

Long-Evans rats (N = 4) maintained on ad lib food and water were initiated to self-administer ethanol using the sucrose-substitution procedure. Following initiation, the rats received IP injections of fluoxetine HCl in sterile water 30 minutes before selected daily self-administration sessions. On other sessions, the rats were injected with sterile water only. Doses of 1, 2, 3, and 5 mg/kg were tested in a random order. Only one drug dose was given each week and each dose was tested at least twice except the 5 mg/kg dose. As dose increased, responding for ethanol decreased with significant reductions at both the 3 and 5 mg/kg dose. The nature of the decrease was such that the duration of continuous responding at the beginning of the session was reduced respective to control and noninjection performance. Overall, the findings of this study support prior work with fluoxetine and other 5-HT blockers which appear to affect satiety mechanisms and possibly reinforcement efficacy.

Administration, Oral

Antagonism of ethanol-reinforced behavior by the benzodiazepine inverse agonists Ro15-4513 and FG 7142: relation to sucrose reinforcement.

The partial inverse benzodiazepine agonist Ro15-4513 has been shown to antagonize many of ethanol's actions, including the reduction of behavior reinforced with ethanol presentation. The studies reported here compared the effects of the Ro compound on sucrose reinforcement alone and concurrently available with ethanol reinforcement. Also, a second inverse agonist, FG 7142, was tested. The result indicated that ethanol reinforcement was more sensitive to the inverse agonists compared to sucrose reinforcement. This was seen as a graded effect upon ethanol responding at doses which failed to have any effect upon sucrose-reinforced behavior. The Ro compound was approximately three times more potent than the FG compound in suppressing ethanol-reinforced responding. Possible explanations for the greater sensitivity of ethanol reinforcement compared to sucrose reinforcement was discussed in terms of ethanol's potential actions at the benzodiazepine-GABA receptor complex.

Animals

Ethanol reinforcement in the alcohol nonpreferring rat: initiation using behavioral techniques without food restriction.

Genetic selection of rats can markedly alter their ethanol consumption. The manner in which environmental factors interact in these genetically selected animals to influence ethanol consumption has not been thoroughly investigated. Using the alcohol-nonpreferring (NP) line of rats selectively bred at the Indiana University School of Medicine, alcohol self-administration in an operant situation was initiated using either a sucrose-fading or a secondary-conditioning procedure. These initiation procedures do not require any food or fluid restriction. Initiation was successful in 10 out of 12 NP animals, with the initiated rats self-administering ethanol at concentrations as high as 40%. Following initiation, a retest of home-cage ethanol preference found increases in ethanol acceptability. When tested in a concurrent operant situation, the initiated NP rats also chose ethanol over water. However, the NP rats had lower alcohol intakes and a different pattern of drinking over time when compared to that of nonselected Long-Evans rats. While the NP rats could be initiated to lever-press for ethanol, at no time did their intake approach that of the selected line of alcohol-preferring (P) rats. Thus, while an upward shift from the genetic baseline in ethanol preference and intake can result from the environmental initiation manipulations employed in these studies, genetic factors would appear to limit the extent to which ethanol ingestion can be increased.

Alcohol Drinking

The relation of initial alcohol experiences to current alcohol consumption in a college population.

Male and female undergraduate college students were surveyed to examine whether age and circumstances of initial taste and intoxication experiences with alcohol would be predictive of current alcohol usage. Age of initiation, nature of the experience (pleasant vs unpleasant), social setting and type of beverage were examined. Only age of initial experience was found to be minimally predictive of subsequent heavier alcohol use. The negative effects of early experiences with alcohol were predictive for abstinence in both sexes, but did not differentiate between moderate and heavy alcohol users in either.

Adult

Adjunctive alcohol drinking in humans.

In an attempt to validate the animal model of adjunctive ethanol drinking in people, human subjects were allowed access to ad lib beer while playing a game that delivered monetary reinforcements on a FI schedule. Subjects exposed to a longer FI schedule drank significantly more than those exposed to a shorter schedule, confirming the prediction made by the animal model. A pattern of ingestion characteristic of adjunctive drinking was also observed in the longer FI condition, providing evidence that ethanol drinking in humans can be schedule-induced.

Adult

Haloperidol and apomorphine effects on ethanol reinforcement in free feeding rats.

Free feeding male Long Evans rats were trained to lever press on a Fixed Ratio 8 schedule for 10% ethanol reinforcement. Mean ethanol intake in 30-minute sessions was 0.38 g/kg. Subcutaneous apomorphine (APO: 0.025 to 0.5 mg/kg) and haloperidol (HAL: 0.005 to 0.0625 mg/kg) administered 15 minutes before sessions dose-dependently reduced responding, but only APO reduced momentary response rates. Low doses of HAL reduced the effect of 0.3 but not 0.05 mg/kg APO. When the rats were food-restricted, control response rates decreased, and APO (0.025 and 0.05 mg/kg) had no further effect. Results were discussed in terms of dopamine involvement in the mechanism of ethanol reinforcement.

Alcohol Drinking

Suppressed ethanol intake by CER following the sucrose-fading initiation procedure.

Lever responding maintained with sweetened ethanol reinforcement (3% sucrose in 10% ethanol) was initiated in food- and water-sated rats with the sucrose-fading procedure. Four tone-shock pairings, one per session, were superimposed on this behavioral baseline [conditioned emotional response (CER) paradigm]. A profound and sustained ethanol response suppression was found. Baseline levels of ethanol responding were recovered by repeating the original initiation procedure. Subsequent exposure to the CS tone alone (no shock) led to a nonsignificant reduction in ethanol responding. These results were discussed in terms of anxiolytic action of ethanol.

Animals