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H H Samson

Publications and source records attributed to H H Samson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Initiation of ethanol self-administration by the sucrose-substitution method with HAS and LAS rats.

This study was performed to examine ethanol self-administration in rats bred for different sensitivities to the sedative effects of alcohol [the Colorado High Alcohol Sensitive (HAS) and Low Alcohol Sensitive (LAS) rats]. Four rats from each replicate line of the HAS and LAS rats (n = 16) were obtained from the University of Colorado, and initiation to self-administer ethanol by the sucrose-substitution procedure was attempted. Before the initiation procedure was conducted, home-cage ethanol intake and preference ratio did not differ between LAS and HAS rats. During the initiation procedure, the LAS rats came to self-administer 10% ethanol (v/v) at similar levels as outbred Wistar rats initiated with the same procedure (approximately 0.4 g/kg/session). The HAS rats, however, failed to initiate (approximately 0.08 g/kg/ session after completing the sucrose-substitution procedure) and lever pressing was reduced even more in the HAS rats when the ethanol concentration presented was > 10% (v/v). Three of the eight HAS rats stopped lever pressing completely when the ethanol concentration was raised to 15%. After initiation, home-cage preference ratio differed significantly between the LAS and HAS rats (LAS > HAS, p < 0.03). That the LAS rats did not consume greater amounts of ethanol compared with outbred Long-Evans or Wistar rats is contrary to our hypothesis, based on recent human data suggesting that a lower sensitivity to ethanol could result in increased alcohol intake. The finding that the HAS rats could not be initiated, while selectively bred ethanol nonpreferring rats can, is also contrary to our hypothesis. Further studies related to ethanol self-administration with the HAS line could provide important information related to the genetics of alcohol nonacceptance.

Alcohol Drinking↗
PubMed1996

Dopamine receptors in the medial prefrontal cortex influence ethanol and sucrose-reinforced responding.

This study tested the role of dopamine receptors in the medial prefrontal cortex (mPFC) in the onset, maintenance, and termination of ethanol and sucrose-reinforced responding. Two groups of Long Evans rats were trained to lever press on a fixed-ratio 4 schedule of reinforcement with 10% ethanol (n = 10) or 5% sucrose (n = 5) presented as the reinforcer. After implantation of injector guide cannulae, the D2/3 agonist quinpirole and the D2 antagonist raclopride were administered bilaterally into the mPFC before behavioral sessions. During control conditions, sucrose reinforcement maintained a 2-fold greater number of responses per session than did ethanol reinforcement. Quinpirole (10.0 micrograms/microliter) reduced total ethanol-reinforced responses by delaying response onset and decreasing the duration of responding, but had no effect on response maintenance (i.e., response rate). A higher dose of quinpirole (20.0 micrograms/microliter) decreased total sucrose responses by simultaneously decreasing duration and response rate, without altering response latency. Thus, the effects of quinpirole on ethanol and sucrose-reinforced responding were similar on response total and duration, but differential on response latency and rate. Raclopride (0.05 and 1.0 microgram/microliter) decreased total ethanol responding and rate, but doses as much as 400-fold greater (20.0 micrograms/microliter) did not alter sucrose response totals. Raclopride alone had no effect on response latency or duration measures in either reinforcement condition. Coadministration of raclopride blocked the quinpirole-induced increase in response latency (ethanol reinforcement) and decrease in response rate (sucrose reinforcement), but had no effect on other response measures. These data are consistent with the interpretation that D2 and D3 receptors in the mPFC are differentially involved in ethanol and sucrose response onset and maintenance, but similarly involved in response termination. However, differences in baseline response parameters and group size may have contributed to the observed effects.

Animals↗
PubMed1995

Morphine induced changes in ethanol-and water-intake are attenuated by the 5-HT3/4 antagonist tropisetron (ICS 205-930).

The opiate agonist morphine has been shown to increase ethanol intake and mesolimbic dopamine (DA) levels. Conversely, the 5-HT3/4 antagonist tropisetron has been shown to decrease ethanol intake and morphine-induced increases in mesolimbic DA levels. This study was designed to test the effects of acutely administered tropisetron on morphine-induced changes in ethanol (6% v/v) and water intake in a two-bottle test procedure. Ten water restricted male rats were injected with combinations of morphine (0.0, 0.56, 1.0, 1.5, 10.0, and 17.0 mg/kg, SC) and tropisetron (0.0, 1.0, 10.0, and 17.0 mg/kg, SC) prior to test sessions. Morphine (1.0 and 1.5 mg/kg) significantly increased absolute (g/kg) and relative ethanol intake (ethanol/total fluid). Tropisetron alone did not affect ethanol or water intake. When tropisetron (10.0 and 17.0 mg/kg) was administered in combination with morphine (1.5 mg/kg), the increase in ethanol intake induced by morphine was attenuated. Tropisetron (1.0 mg/kg) reversed a decrease in ethanol intake induced by morphine (17.0 mg/kg). The two highest doses of tropisetron partially attenuated a significant decrease in water intake produced by morphine (17.0 mg/kg). These data suggest that opiate and 5-HT3 mechanisms could interact in the regulation of ethanol intake. However, the doses of tropisetron tested were high and, therefore, the potential involvement of 5-HT4 receptors or other neurotransmitter systems in regulating ethanol intake is discussed.

Alcohol Drinking↗
PubMed1995

GABAergic transmission in the nucleus accumbens is involved in the termination of ethanol self-administration in rats.

Long-Evans rats (n = 12) were trained to lever-press on a fixed-ratio 4 schedule of reinforcement with ethanol (10% v/v) presented as the reinforcer. After implantation of bilateral stainless-steel guide cannulae aimed at the nucleus accumbens, site-specific microinjections of muscimol (1-30 ng) and bicuculline (1-10 ng) were tested for effects on ethanol-reinforced responding. Baseline response patterns were characterized by initial high rates that terminated abruptly after approximately 20 min. Muscimol administration in the nucleus accumbens decreased the total number of ethanol-reinforced responses and obtained reinforcers. Bicuculline also decreased ethanol-reinforced responses and reinforcers at the highest dose tested. When a dose of bicuculline (1 ng) that was ineffective by itself was coadministered with an effective dose of muscimol (10 ng), the muscimol-induced decreases in responding were blocked. Analysis of response patterns showed that muscimol decreased ethanol self-administration by terminating responding, normally lasting 20 min, after approximately 10 min with no changes in local response rate. Bicuculline decreased total responding by producing parallel, but nonsignificant, changes in time course and response rate. These data suggest that GABAergic transmission in the nucleus accumbens is involved in the termination, but not the onset or maintenance of ethanol self-administration. The specificity of this effect gives emphasis to the importance of measuring behavioral parameters, as well as products of behavior (such as intake volume) in the study of ethanol self-administration.

Alcohol Drinking↗
PubMed1995

Sucrose, ethanol, and sucrose/ethanol reinforced responding under variable-interval schedules of reinforcement.

Adding sweeteners to ethanol solutions is a common method of inducing rats to consume ethanol. However, it has usually been assumed that it is the sweet taste and/or the calories contained in the sweet solution that controls consumption. The present experiment examined the role of ethanol in controlling responding reinforced by ethanol or an ethanol/sucrose mixture compared with sucrose solutions of various concentrations. After initiation to self-administer 10% (v/v) ethanol using the sucrose-substitution method, rats were trained to respond under a concurrent VI 5" VI 5" schedule. During one condition, responding on one lever was reinforced by the presentation of 10% ethanol, and responding on a second lever was reinforced by water or one of the following sucrose solutions: 1% (w/v), 1.5%, 2%, 2.5%, 3%, and 5%. During a subsequent condition, responding reinforced by a 10% ethanol/2% sucrose mixture was compared under the concurrent schedule with responding reinforced by water, 2%, 2.5%, 3%, 5%, or 10% sucrose (w/v). The results indicated that the ethanol or ethanol/sucrose mixture maintained more responding than did sucrose solutions that were sweeter. Data support the conclusion that, after initiation, the taste and/or pharmacological effects of ethanol had become an important component of the reinforcing stimulus independent of the sweetener.

Alcohol Drinking↗
PubMed1994

Effects of intraaccumbens injections of dopamine agonists and antagonists on sucrose and sucrose-ethanol reinforced responding.

The present experiment tested the effects of intraaccumbens injections of dopamine (DA) agonists and antagonists on operant responding reinforced by sucrose and sucrose/ethanol solutions. The mixed DA agonist d-amphetamine (20.0 micrograms/microliters) significantly reduced responding reinforced by a low concentration sucrose solution (2% w/v) by 48% and 38% compared to no injection and sham control values, respectively. The addition of ethanol (10%) to a low concentration sucrose solution (3%) presented as the reinforcer changed the response pattern from a continuous moderate response rate, over a 30 min session, to an initial high response rate that terminated after approximately 10 min. With sucrose/ethanol reinforcement, d-amphetamine slowed the initial high response rate but extended responding throughout the 30 min sessions. However, no significant changes were observed in number of responses per session. When 75% sucrose (w/v) was presented as the reinforcer, d-amphetamine did not change the total number of responses/session, but response patterns were again altered from high initial rates with early offset to slow steady rates that continued for the duration of sessions. The D2 DA antagonist raclopride (0.1-5.0 micrograms/microliters) resulted in a dose-dependent decrease in responding reinforced by 75% sucrose. The baseline patterns, response totals, and effects of the DA antagonists resemble our previously reported findings with 10% ethanol (v/v) reinforcement. These data support the conclusion that mesolimbic DA activity may be a common mechanism in ethanol reinforced behavior and behavior reinforced by other substances, but suggest that the nature of behavioral change may depend upon the reinforcer.

Animals↗
PubMed1993

Effect of dopamine agonists and antagonists on ethanol-reinforced behavior: the involvement of the nucleus accumbens.

Rats initiated to self-administer 10% ethanol (v/v) in an operant situation using the sucrose-substitution technique received bilateral n. accumbens or caudate nucleus microinjections of d-amphetamine (4, 10, and 20 micrograms/brain), quinpirole (4 micrograms/brain), and/or raclopride (0.1, 0.5, and 1.0 micrograms/brain). Only microinjections into the n. accumbens produced changes in rate and pattern of responding. With d-amphetamine, an increase in total responding and a slowing of initial response rate was seen, whereas with raclopride administration a dose-related decrease in total responding was observed with no alteration in momentary response rates. Drug-dependent behavioral rate and pattern differences suggest that DA activity in the n. accumbens influences ethanol reinforced behavior.

Analysis of Variance↗
PubMed1993

Effects of ethanol concentration and fixed-ratio requirement on ethanol self-administration by P rats in a continuous access situation.

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. During Experiment 1, the effects of changing ethanol concentration and response requirement for ethanol were examined. Ten percent and 20% ethanol (v/v) were available on two fixed ratio (FR) schedules, FR 1 and FR 4, for 2 weeks each. During Experiment 2, the effects of increasing the response requirement for ethanol were investigated. Starting with FR 4, the FR requirement for ethanol doubled during 2-week intervals until FR 32 was in effect. For the final phase of these studies, water was placed in the dipper for 1 week followed by a return to 10% ethanol in the dipper. The results from Experiment 1 indicated that when the FR requirement was decreased from FR 4 to FR 1, ethanol-reinforced responding decreased but total daily intake increased. Lowering the FR requirement did not affect the number of ethanol bouts per day but bout size increased. Ethanol concentration had no effect on bout size but the number of bouts per day decreased when the concentration was increased to 20%. Since bout size was unchanged by increasing the ethanol concentration, intake per bout increased at 20% ethanol. The results from Experiment 2 indicated that increasing the response requirement for ethanol decreases ethanol intake. When water was placed in the dipper, responding decreased to the lowest levels observed in the experiment. When ethanol was returned to the dipper, responding returned to baseline levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1993

Ventral tegmental microinjections of quinpirole decrease ethanol and sucrose-reinforced responding.

The effects of microinjections in the ventral tegmental area (VTA) of the dopamine D2/D3 agonist quinpirole on ethanol- and sucrose-reinforced responding were tested. Two groups of Long-Evans rats were trained to lever press on a fixed-ratio 4 schedule with 10% ethanol (v/v) (n = 8) and 75% sucrose (w/v) (n = 10) presented as the reinforcer. Weekly bilateral injections of quinpirole were tested in the ethanol group (0.0, 0.001, 0.01, 0.1, and 1.0 micrograms/microliters) and sucrose group (0.0, 0.01, 0.1, 1.0, and 10.0 micrograms/microliters). Quinpirole dose dependently decreased ethanol- and sucrose-reinforced responding, but the dose-effect curve for sucrose was shifted two orders of magnitude to the right of the ethanol curve. Temporal response patterns during control sessions for both reinforcers were characterized by initial high rates that terminated after approximately 10 min. VTA injections of quinpirole dose dependently delayed the onset of the first response and the initial high rate period, and resulted in an early termination of responding following onset. These data support the hypothesis that dopamine activity in the VTA is involved in the regulation of ethanol-reinforced responding in a manner similar to that of other reinforcers.

Animals↗
PubMed1993

Effects of manipulating food availability on ethanol self-administration by P rats in a continuous access situation.

Male rats from the alcohol-preferring (P) line were housed in operant chambers in which food, water, and ethanol (10% v/v) were available continuously 23 hr per day. Over a period of weeks, the fixed ratio (FR) requirement for food reinforcement was gradually increased from FR 1 to FR 64. The response requirements for water and ethanol remained constant throughout the experiment. As the FR requirement for food reinforcement increased, the total number of food-reinforced responses increased significantly, whereas the total number of food pellets delivered per day and total calories per day decreased significantly. Conversely, ethanol intake (g/kg) and the percentage of total calories from ethanol increased significantly as the response requirement for food reinforcement increased. The increase in ethanol intake was accounted for largely by an increase in the number of ethanol drinking bouts per day rather than an increase in the number of dippers presented per bout. The results support the hypothesis that the manipulation of environmental variables, such as FR requirement for food reinforcement, can influence the ethanol self-administration of P rats; an effect observed previously with nonselected Long-Evans rats.

Alcohol Drinking↗
PubMed1993

The role of the mesoaccumbens dopamine system in ethanol reinforcement: studies using the techniques of microinjection and voltammetry.

Microinjection of dopamine agonists and antagonists into both the n. accumbens and the ventral tegmental area were shown to alter ethanol reinforced responding. These data support that of others researchers in showning that the mesolimbic pathway is involved in the mechanisms underlying ethanol reinforcement. Studies using microvoltammetry suggest that ethanol's access into this pathway is not by direct stimulation of DA release from the terminal fields in the n. accumbens.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗