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F O Risinger

Publications and source records attributed to F O Risinger.

32 records · Page 2Linked to original sources
PubMed1992

Haloperidol does not alter expression of ethanol-induced conditioned place preference.

A recent experiment (Risinger et al., Psychopharmacology, 107 (1992) 453-456) has shown that haloperidol does not prevent acquisition of ethanol-induced conditioned place preference, suggesting that dopaminergic mechanisms do not mediate the primary rewarding properties of ethanol. The present experiment examined whether haloperidol would prevent the expression of conditioned reward to ethanol-paired stimuli using the place conditioning paradigm. DBA/2J mice received four pairings of a tactile stimulus with ethanol (2 g/kg, IP). A different stimulus was paired with saline. Before preference testing, different groups received one of three doses of haloperidol (0, 0.05 or 0.1 mg/kg); ethanol was not given. Haloperidol produced a dose-dependent decrease in locomotor activity, but did not affect conditioned place preference. These results suggest that expression of ethanol-induced conditioned place preference is mediated by non-dopaminergic mechanisms.

Animals↗
PubMed1992

Haloperidol reduces ethanol-induced motor activity stimulation but not conditioned place preference.

This experiment examined the impact of a dopamine receptor blocker on ethanol's rewarding effect in a place conditioning paradigm. DBA/2J mice received four pairings of a tactile stimulus with ethanol (2 g/kg, IP), haloperidol (0.1 mg/kg, IP)+ethanol, or haloperidol alone. A different stimulus was paired with saline. Ethanol produced increases in locomotor activity that were reduced by haloperidol. However, conditioned preference for the ethanol-paired stimulus was not affected by haloperidol. Haloperidol alone decreased locomotor activity during conditioning and produced a place aversion. These results indicate a dissociation of ethanol's activating and rewarding effects. Moreover, they suggest that ethanol's ability to induce conditioned place preference is mediated by nondopaminergic mechanisms.

Animals↗
PubMed1992

Context-drug pairings enhance tolerance to ethanol-induced disruption of operant responding.

Much of the research implicating learning in the development of tolerance to ethanol-induced impairment has used an experimental design in which different groups receive drug either before or after an opportunity to perform an instrumental or operant task. The stronger tolerance observed in subjects who perform while intoxicated is most often attributed to the reinforced practice of a learned compensatory response. Using an experimental procedure modeled after Chen (1979), the present study examined an alternative theoretical basis for tolerance in the before-versus-after design. Specifically, the effects of Pavlovian context-drug pairings were assessed under circumstances that precluded reinforced practice of the operant response. Three groups of food-deprived rats were initially trained to barpress for sucrose on an FR15 schedule. After 30 sessions, the bar was retracted and the dipper was covered for a 3-day tolerance acquisition phase. During this phase, each group received an IP injection 15 min before and 45 min after each session. The Paired group received ethanol (1.2 g/kg) before and saline after the session, thus pairing ethanol with cues of the test chamber. The Unpaired group received saline before and ethanol after the session, while the No-Drug group always received saline. During a final test phase, all groups received ethanol (1.5 g/kg) before access to sucrose on the FR schedule. The Paired group completed the first FR15 sequence more rapidly than either control group, indicating that context-ethanol pairings enhanced tolerance to the drug's disruptive effect on the initiation of operant responding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Genetic differences in ethanol-induced hyperglycemia and conditioned taste aversion.

Genetic differences in the hyperglycemic response to acute ethanol exposure and ethanol-induced conditioned taste aversion were examined using inbred mice. Adult male C57BL/6J and DBA/2J mice were injected with ethanol (0-6 g/kg, I.P.) and blood glucose levels determined over 4 h. C57 mice demonstrated greater dose-dependent elevations in blood glucose compared to DBA mice. In a conditioned taste aversion procedure, water deprived mice received ethanol injections (1-4 g/kg, I.P.) immediately after access to a NaCl flavored solution. DBA mice developed aversion to the ethanol-paired flavor at a lower dose (2 g/kg) than C57 mice. These results provide further support for a possible inverse genetic relationship between sensitivity to ethanol-induced hyperglycemia and sensitivity to conditioned taste aversion.

Animals↗
PubMed1992

Effect of Ro 15-4513 on ethanol-induced conditioned place preference.

The benzodiazepine receptor inverse agonist Ro 15-4513 reverses a number of ethanol's effects, including its reinforcing properties as measured through self-administration. The present study examined the effect of this putative ethanol antagonist in a place conditioning design that has been shown to be sensitive to ethanol's rewarding properties in mice. Using an unbiased differential conditioning procedure, DBA/2J mice received, on alternate days, pairings of a distinctive floor stimulus (CS+) with either ethanol (2 g/kg), Ro 15-4513 (3 mg/kg), or a combination of ethanol and Ro 15-4513. On alternate days, a different distinctive floor stimulus (CS-) was paired with vehicle. Under these conditions, ethanol produced a conditioned place preference that was unaffected by Ro 15-4513. Ro 15-4513 alone did not produce either a place preference or aversion. Ro 15-4513 did produce reductions in locomotor activity during conditioning, indicating it was behaviorally active. These results indicate that a dose of Ro 15-4513 that alters general activity does not affect ethanol reward.

Animals↗
PubMed1991

Assessment of ethanol's hedonic effects in mice selectively bred for sensitivity to ethanol-induced hypothermia.

Mice selectively bred for sensitivity (COLD) or insensitivity (HOT) to the hypothermic effect of ethanol were tested in three tasks purported to assess ethanol's hedonic properties: place conditioning, taste conditioning, and ethanol drinking. In the place conditioning task, distinctive tactile (floor) stimuli were differentially paired with injection of ethanol (2.25 g/kg) or saline, and preference for the tactile stimuli was assessed during a choice test without ethanol. In the taste conditioning task, fluid-deprived mice were given repeated access to saccharin followed by injection of ethanol (2.25 g/kg). In the drinking task, mice were given access on alternate days to a single drinking tube containing water or ethanol in a concentration that gradually increased from 1 to 12% (v/v) over days. HOT mice showed greater conditioned preference for ethanol-paired flavor cues, and greater aversion for ethanol-paired flavor cues, and drank less ethanol at concentrations above 5% than COLD mice. HOT mice also showed higher levels of ethanol-stimulated activity than COLD mice. Control experiments indicated that the lines did not differ in initial preference for the tactile and flavor stimuli used in the conditioning tasks. Because the same line differences were seen in mice selected from two genetically independent populations, these studies offer strong evidence of genetic correlations between ethanol's thermal effect and its effect on activity, place conditioning and taste conditioning. Evidence of a genetic correlation between ethanol's thermal effect and ethanol drinking, however, is weaker since it is based on a line difference observed in only one of the genetic replicates. (ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1991

The relationship between ethanol-induced hyperglycemia and hypothermia: evidence of genetic correlation.

The hyperglycemic and hypothermic responses to acute ethanol exposure (0, 2, 4, 6 g/kg, intraperitoneally) were examined in non-fasted mice selectively bred for sensitivity (COLD line) or insensitivity (HOT line) to ethanol-induced hypothermia. Blood samples and rectal temperatures were obtained immediately before injection and hourly for 4 hr after injection. As expected, COLD mice demonstrated greater and more prolonged reductions in body temperature than HOT mice, especially at the 4 g/kg dose (HOT: -2.58 degrees C, COLD: -5.08 degrees C). Ethanol produced significant dose-dependent elevations in blood glucose levels over the 4-hr sampling period in both lines. The greatest elevations in blood glucose levels were seen at 4 g/kg, with COLD mice (mean = 225.1 mg/dl) showing significantly greater elevations in blood glucose levels compared to HOT mice (mean = 177.0 mg/dl). These results support the hypothesis that the thermic and glycemic effects produced by ethanol are due to related neural processes that share a common genetic component.

Animals↗
PubMed1985

Reduction of flurazepam convulsive threshold by Ro 15-1788.

The influence of the benzodiazepine (BZ) receptor antagonist Ro 15-1788 on the convulsant properties of flurazepam (FLZ) was studied in rats. Animals were prepared with chronic epidural electrodes for EEG recording and respiratory rates were recorded via a rubber bulb connected to a pressure transducer. FLZ convulsive thresholds were determined by continuous IV infusion in the presence and absence of Ro 15-1788 pretreatment. All animals receiving the FLZ infusion experienced convulsions preceded by dose-dependent reduction of respiratory rate. Pretreatment with Ro 15-1788 substantially reduced the FLZ convulsive threshold, suggesting a blockade of the depressant (anticonvulsant) aspect of the FLZ effect, thus, augmenting a convulsant effect at a separate receptor. An alternate hypothesis is that Ro 15-1788 may increase the affinity or intrinsic activity of the receptor responsible for the convulsant aspect of FLZ. Ro 15-1788 did not appear to alter the respiratory rate depressant effect of FLZ, although early onset of convulsions in the pretreated animals precluded measurement of respiration at the higher dose of FLZ allowable in animals that were not pretreated with the antagonist.

Animals↗
PubMed1984

[14C]normacromerine fate in the rat.

The biological fate of [14C] normacromerine , a dimethoxylated phenethylamine derivative with putative hallucinogenic properties, was evaluated in male Sprague-Dawley rats at 100 mg/kg po. Urine was the primary elimination route accounting for 50% of administered carbon-14 after 24 h. Of this urine radioactivity, normacromerine comprised 30% at 8 h decreasing to nondetectable levels at 24h. Carbon-14 in feces represented less than 10% of the administered dose at 24 h, and 14CO2 expiration was not detected. Studies of normacromerine fate in comparison with previously studied phenethylamines may enhance evaluation of hallucinogenic potential of normacromerine .

Alkaloids↗
PubMedDate not supplied

Nicotine-induced conditioned place preference and conditioned place aversion in mice.

The motivational effects of nicotine were examined in mice using an unbiased place conditioning design. Swiss-Webster mice received four 15-min parings of a tactile stimulus with different doses of nicotine (0.25-2.0 mg/kg, IP). A different tactile stimulus was paired with saline injections. During conditioning, nicotine produced locomotor depression at the 2.0-mg/kg dose, with the greatest reduction in activity occurring during the latter part of each nicotine conditioning session. After four trials, nicotine produced increases in locomotor activity during the initial part of the nicotine sessions at doses 0.5 mg/kg or above. Upon testing, nicotine-induced conditioned place preference was noted in mice receiving 0.5 mg/kg nicotine. Conditioned place aversion was noted in mice receiving 2.0 mg/kg nicotine whereas doses of 0.25 and 1.0 mg/kg produced no conditioning. These results indicate that nicotine has dose-dependent rewarding and aversive effects measured in an unbiased place conditioning paradigm using mice.

Animals↗
PubMedDate not supplied

Genetic differences in ethanol-induced conditioned taste aversion after ethanol preexposure.

The present studies examined the development of ethanol-induced conditioned taste aversion in C57BL/6J (B6) and DBA/2J (D2) mice with a history of ethanol preexposure. In Experiment 1, adult male B6 and D2 mice received four preexposure injections of either saline or 4 g/kg ethanol over an 8-day period. After preexposure, all mice were given five conditioning trials consisting of 1-h access to 0.15% w/v saccharin solution followed immediately by ethanol injections (4 g/kg, IP) on all but the last trial. Drug-naive D2 mice showed greater reductions in saccharin intake. Ethanol preexposure reduced the development of ethanol-induced taste aversion in each strain. However, B6 mice showed little taste aversion overall, hindering the characterization of genetic differences in ethanol's preexposure effect. To address this problem, the parameters for taste conditioning were changed in Experiment 2 to more closely match degree of taste aversion in drug-naive mice across both strains. B6 and D2 mice received four preexposure injections of either saline, 2 g/kg ethanol, or 4 g/kg ethanol, or 4 g/kg ethanol. Subsequently, mice received five conditioning trials consisting of 1-h access to 0.2 M NaCl flavor followed by 4 g/kg ethanol (B6 mice) or 2 g/kg ethanol (D2 mice) on trials 1-4. Ethanol-naive mice of each strain developed similar levels of conditioned taste aversion. Ethanol preexposure produced greater retardation of conditioned aversion in B6 mice than in D2 mice. These results demonstrate genetic differences in the ability of ethanol preexposure to reduce the development of ethanol-induced conditioned taste aversion.

Animals↗
PubMedDate not supplied

Effects of haloperidol or SCH-23390 on ethanol-induced conditioned taste aversion.

Dopaminergic systems are thought to play an important role in the motivational effects of ethanol. The present experiments examined the effects of haloperidol (a D2 antagonist) and SCH-23390 (a D1 antagonist) on the acquisition of ethanol-induced conditioned taste aversion. In four separate experiments, adult male Swiss-Webster mice were acclimated to a 2-h/day water restriction regimen. Subsequently they received four conditioning trials consisting of 1-h access to either 0.2 M NaCl (experiments 1-3) or 0.15 % w/v saccharin (experiment 4). After flavor access on trials 1-3, subjects received either haloperidol (0.1, 0.15, or 0.3 mg/kg), SCH-23390 (0.05 mg/kg), or saline followed 30 min later by 0, 2, or 4 g/kg ethanol. Ethanol-flavor pairings reduced subsequent flavor intakes, indicating the development of conditioned taste aversion. Neither haloperidol of SCH-23390 reduced flavor intakes in the absence of ethanol. However, both haloperidol and SCH-23390 reduced ethanol-conditioned aversion depending on ethanol dose and conditioned flavor. These results are consistent with the notion that dopaminergic processes are important for the development of ethanol-induced conditioned taste aversion, and the notion that dopaminergic receptor systems influence both positive and negative motivational effects of ethanol.

Animals↗
PubMedDate not supplied

Quantitative trait loci for acute behavioral sensitivity to paraoxon.

Genetic mechanisms responsible for organophosphate (OP)-induced behavioral changes remain obscure. In the present study, provisional quantitative trait loci (QTL) associated with acute sensitivity or insensitivity to hypolocomotion produced by the OP paraoxon were identified. Naive adult male and female mice of the BXD/Ty series (22 different BXD strains plus C57BL/6J and DBA/2J progenitor strains) received 0 or 0.25 mg/kg paraoxon (IP), immediately before placement in an activity chamber for a 30-min test. As expected, based on dose-response and time course studies with Swiss-Webster, C57BL/6, and DBA/2 mice, paraoxon treatment reduced locomotor activity in most, but not all BXD strains. Heritability (proportion of phenotypic variability attributed to genetic differences) was 0. 58 for the paraoxon treatment effect. Difference scores (strain mean for vehicle activity minus strain mean for paraoxon activity), and percent change in activity of paraoxon-treated mice compared to vehicle-treated mice were calculated for each BXD strain. QTL analyses using activity difference scores and percentage change in activity were conducted using a database with over 1300 unique genetic markers. Several provisional QTL found on different chromosomes were associated with the activity phenotype. Of these, several markers attained p<0.01 or greater. These were as follows: Chr 1: Ly9, p<0.006; Chr 6: D6Ncvs44, p<0.0005; Chr 9: D9Mit15, p<0. 003; Chr 11: D11Ncvs76, p<0.002; Chr 15: Tstap198, p<0.008. In addition, several markers on chromosome 3 approached p<0.01. Identified genes found near these regions include two plasma carboxylesterase alleles on chromosomes 6 and 9, a glutamate receptor subtype on chromosome 11 and a glycine receptor subunit on chromosome 11, raising the possibility that these genes could be the basis for these provisional QTLs.

Animals↗