Biomedical subjects

C W Hodge

Publications and source records attributed to C W Hodge.

10 recordsLinked to original sources

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↗

PubMed1994

Comparison of the discriminative stimulus function of ethanol following intracranial and systemic administration: evidence of a central mechanism.

Rats were trained using a two-lever drug discrimination procedure to press one lever following systemic administration of ethanol (1.0 mg/kg, IP) and another lever following IP injections of saline. After determination of an ethanol generalization curve (0.25-1.25 g/kg, IP), rats were surgically implanted with bilateral stainless steel guide cannulae that terminated in the lateral ventricles. Following surgery, the generalization curve was redetermined and did not differ from presurgery values. Then, generalization to bilateral intracerebroventricular (ICV) injections of ethanol (600.0 and 900.0 mM, 1.0 microliter/side) were administered alone and in combination with IP injections of ethanol. The ICV ethanol injections produced partial generalization, but the combination of ICV ethanol (600.0 and 900.0 mM) with IP ethanol (0.25 and 0.50 g/kg) injections were two- to threefold more potent then IP injections alone. Response rates were unaffected by any dose of ethanol tested. These data suggest central mediation of ethanol's discriminative stimulus function due to: 1) increased potency of systemically administered ethanol by centrally administered ethanol, and 2) partial generalization between centrally and peripherally administered ethanol.

Animals↗

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

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

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

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↗

PubMedDate not supplied

Effects of morphine on acquisition and maintenance of ethanol and water intake patterns in rats.

Two experiments were conducted to assess the effects of chronic subcutaneous injections of morphine (1.0 mg/kg) or saline on the pattern and amount of sweetened ethanol and water intake in fluid restricted Long-Evans rats. Following daily injections, 2-h two-bottle choice tests were conducted with water and an ethanol solution (15% ethanol v/v in 5% sucrose w/v). During a 20-day acquisition phase (Experiment 1), ethanol intake patterns and amounts did not differ between saline (n = 6) and morphine (n = 6) groups. Both groups exhibited ethanol intake patterns that decreased exponentially throughout the session suggesting control by fluid restriction procedures. Morphine decreased water intake during initial periods of each session and increased intake during later periods. In Experiment 2, morphine and saline injections were reversed across three phases with the same rats. Morphine increased total ethanol consumption during the first few days of each 15-day phase, but the groups did not differ thereafter, and the initial increases produced no statistically significant group differences. Additionally, morphine augmented ethanol intake in early portions of sessions, while water intake was decreased and increased during early and later portions of each session, respectively. Analysis of the data from the last 5 days of each phase indicated that, when injected with morphine, the group which received saline during acquisition consumed significantly more ethanol solution than the group injected with morphine during acquisition. The effect on patterns of water and ethanol intake were observed, regardless of the drug injected during acquisition.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

PubMedDate not supplied

Specific decreases in ethanol- but not water-reinforced responding produced by the 5-HT3 antagonist ICS 205-930.

The serotonin 5-HT3 antagonist ICS 205-930 has been shown to block the discriminative stimulus properties of ethanol and decrease voluntary intake, suggesting a possible role for 5-HT3 systems in the reinforcing effects of ethanol. ICS 205-930 (0.56, 1.0, 3.0, 10.0, and 17.0 mg/kg i.p.) was examined on ethanol and water self-administration in an operant paradigm. Following a sucrose-fading procedure, two groups of nondeprived rats responded on either a concurrent fixed ratio 4 schedule for ethanol (10% v/v) and water (CONC FR4 FR4), or a single FR4 schedule for ethanol (10% v/v). ICS 205-930 dose-dependently decreased ethanol-reinforced responding in the concurrent condition without decreasing water-reinforced responding, suggesting a specific effect on ethanol. Ethanol-reinforced responding was also dose-dependently decreased in the single FR4 condition, but the dose effect curve was shifted to the left. These data support the conclusions that 5-HT3 systems may play a specific role in ethanol self-administration that is independent of general appetitive and motor processes, and that 5-HT3 antagonists may have therapeutic efficacy in the treatment of alcohol abuse when multiple reinforcers are available.

Alcohol Drinking↗