Biomedical subjects

Anthony L Riley

Publications and source records attributed to Anthony L Riley.

12 recordsLinked to original sources

PubMed2004

Morphine- and cocaine-induced c-Fos levels in Lewis and Fischer rat strains.

Lewis (LEW) and Fischer 344 (F344) rat strains have been reported to differ in their sensitivity to the rewarding and aversive effects of both cocaine and morphine. Specifically, LEW rats self-administer morphine and cocaine to a greater extent than F344 rats, while LEW (compared to F344) rats are more sensitive to the aversive effects of cocaine but less sensitive to the aversive effects of morphine. Consistent with assessments of the rewarding effects of morphine and cocaine in these two strains, LEW rats have lower basal, and generally higher drug-induced, activity in brain regions associated with reward. Although the brain areas that mediate the aversive effects of drugs are becoming better defined, no studies have compared the activation of these areas by aversion-inducing drugs in the LEW and F344 strains. As such, the relationship between the ability of drugs to activate these aversion-associated brain areas and to induce a conditioned taste aversion (CTA) in these strains is unknown. To explore this relationship, LEW and F344 rats were injected with saline or doses of morphine or cocaine (32 mg/kg for both drugs) that have been shown to generate differential taste aversion learning in these strains. All animals were subsequently tested for c-Fos expression in areas of the brain associated with aversion learning (the lateral and medial parabrachial nucleus, intermediate and caudal nucleus tractus solitarius and area postrema), reward (the shell of the nucleus accumbens) and locomotion (the core of the nucleus accumbens and the caudate putamen). The present results indicated that patterns of morphine- and cocaine-induced c-Fos within CTA-associated, but not reward- or locomotor-associated, brain regions paralleled the differential behavioral sensitivities of LEW and F344 rats to these drugs within CTA learning. Analyses with other drugs that do and do not induce aversions differentially would further assess the role of these brain areas in aversion learning, in general, and in strain-dependent differences, in particular.

Analgesics, Opioid↗

PubMed2004

Conditioned taste aversion: a database.

The present commentary describes the availability of a database on conditioned taste aversion learning, the avoidance of fluids and foods previously associated with the aversive effects of a variety of drugs. The database includes articles as early as 1955 by Garcia and his colleagues [Science 122 (1955) 127] (reporting such avoidance in rats) and papers just published given that the database is ongoing and constantly updated. At the printing of this announcement, approximately 2600 papers are included in the database. The database allows the user to search for articles by author(s), key word(s), date, title and journal. These terms can be used as single entries or multiple combinations. Finally, the full database can be viewed by performing the search function without entering any terms in the query window. The database can be accessed at http://www.CTALearning.com.

Animals↗

PubMed2004

Cocaine, but not alcohol, reinstates cocaine-induced place preferences.

Alcohol has been reported to modulate the reinforcing and aversive properties of cocaine. Given these effects, the present study examined whether this interaction could be extended to cocaine seeking using the conditioned place preference (CPP) procedure. Specifically, 31 drug-naive, male Sprague-Dawley rats were injected every other day (for 8 days) with either 20 mg/kg cocaine or vehicle in an alternating sequence prior to being restricted to a drug or vehicle side of a place preference chamber for 30 min. On Day 9, subjects were given 15-min access to the entire chamber to assess compartment preference. Animals then underwent extinction by pairing both compartments with vehicle for an additional 8 days. Extinction was assessed in the same manner as place conditioning. The animals were then given priming injections of vehicle, 15 mg/kg cocaine, 0.5 or 1.0 g/kg alcohol on the day following the extinction test. Pairing 20 mg/kg cocaine with a specific compartment resulted in a significant place preference. Breaking the relation between the compartment and the drug by pairing both compartments with vehicle extinguished this preference. Interestingly, only 15 mg/kg cocaine was able to reinstate the cocaine-induced place preference, suggesting that the ability to reinstate cocaine seeking may be drug specific.

Animals↗

PubMed2004

Lithium-chloride-induced conditioned taste aversions in the Lewis and Fischer 344 rat strains.

Conditioned taste aversions (CTAs) are differentially induced by cocaine and morphine in the Lewis and Fisher 344 (LEW and F344, respectively) rat strains. Although the acquisition of LiCl-induced aversions has recently been reported to be comparable between the two strains, these aversions were induced by the oral consumption of LiCl, and the possibility exists that, given their different weights, that differential doses were functionally administered. To address the issue of LiCl-induced aversions in LEW and F344 rats (and to control for this possible confound), the present study assessed the ability of intraperitoneally (ip) administered LiCl to induce aversions in the two strains. Specifically, rats from both strains were given 20-min access to saccharin and injected immediately, thereafter, with 0.3, 0.6, 0.9 or 1.2 mEq/kg, 0.15 M LiCl (or its distilled water vehicle). Under these conditions, both strains acquired dose-dependent aversions that increased over repeated trials. Although there was no overall strain difference in LiCl-induced aversions, LEW rats displayed a stronger aversion at the 0.3 mEq/kg dose (on Trial 3) and acquired the aversion at this dose more rapidly than the F344 rats did (by Trial 2 vs. Trial 3). Although evident, this strain difference with LiCl does not parallel that reported with morphine (in which F344 rats are more sensitive than LEW rats) or with cocaine (in which the differences between LEW and F344 rats are larger and occur at more doses and on more trials). These cross-drug comparisons suggest that strain differences in aversion learning are drug dependent. Because drug acceptability has been reported to be a function of the balance between the reinforcing and aversive effects of various compounds, the examination of possible strain differences in aversion learning with a range of such compounds may provide insight into drug acceptability (and use) in these strains.

Animals↗

PubMed2004

The modulation of cocaine-induced conditioned place preferences by alcohol: effects of cocaine dose.

Busse and Riley [Biol. Psychiatry 26 (2002) 1373] have recently reported that alcohol dose dependently attenuated cocaine-induced place preferences. Although the mechanism for this effect is not known, it is possible that it is due to alcohol potentiating the aversive properties of cocaine, a potentiation that masks or abates cocaine's rewarding effects in this preparation. Given that the affective properties of cocaine (both aversive and rewarding) have been reported to be dose dependent, it might be expected that alcohol's ability to affect cocaine-induced place preferences would be influenced by changes in cocaine dose. To address this possibility, the following experiments assessed the effects of alcohol (0.5 g/kg) on place preferences induced by high (20, 30 and 40 mg/kg: Experiment 1) and low (2.5 and 5 mg/kg; Experiment 2) doses of cocaine. Specifically, every other day for four cycles male Sprague-Dawley rats were injected with cocaine, alcohol or one of several cocaine/alcohol combinations immediately before being placed on one side of a two-compartment place preference chamber. On alternate days, they were placed on the other side of the chamber after being injected with the drug vehicle(s). In Experiment 1, all doses of cocaine (20, 30 and 40 mg/kg) produced a significant preference for the drug-paired compartment, whereas alcohol alone produced no effect. When given in combination, alcohol attenuated the cocaine-induced place preference (at 30 and 40 mg/kg cocaine). In Experiment 2, neither cocaine (2.5 or 5 mg/kg) nor alcohol produced a significant effect when given alone. However, animals receiving the combination of alcohol and cocaine (5 mg/kg) displayed a significant place preference. These findings indicate that alcohol can both weaken and strengthen cocaine-induced place preferences, possibly via its effects on the rewarding and aversive properties of cocaine. The effect of alcohol is dependent on the dose of cocaine.

Animals↗

PubMed2003

Morphine-induced conditioned taste aversions: assessment of sexual dimorphism.

Although sex differences in taste aversions have been reported with emetics such as lithium chloride (LiCl), little is known whether such findings generalize to other aversion-inducing drugs, including recreational compounds. One particular class of recreational compounds that induces taste aversions but that has not been examined for sex differences in its aversive properties is the opioids. To assess sex differences in the aversive properties of the opioids, Experiment 1 examined the acquisition and extinction of morphine-induced taste aversions in male and female rats. To determine whether the specific parametric conditions used in Experiment 1 would support sex differences in general, Experiment 2 examined possible sex differences in the acquisition and extinction of LiCl-induced taste aversions, a compound for which sex differences have been previously reported. During acquisition, male and female rats were given 20-min access to a novel saccharin solution and injected with either morphine (0, 10, 18 and 32 mg/kg s.c.; Experiment 1) or LiCl (0, 0.3, 0.6 and 1.2 mEq s.c.; Experiment 2) every fourth day for a total of four conditioning trials. During extinction, subjects were allowed access to saccharin but were not injected (for a total of eight trials). There were no sex differences in acquisition with either morphine or LiCl. There were also no sex differences in extinction with morphine; however, sex differences were found with LiCl, an effect consistent with prior assessments with this drug. The basis for and implications of the differences in the effects of sex on morphine- and LiCl-induced taste aversions were discussed.

Analgesics, Opioid↗

PubMed2003

Strain-dependent differences in schedule-induced polydipsia: an assessment in Lewis and Fischer rats.

Strain-dependent differences have been used to highlight unknown genetic contributions to important behavioral and physiological end points. In this regard, the Fischer (F344) and Lewis (LEW) rat strains have often been studied because they exhibit a myriad of behavioral and physiological differences. Recently, schedule-induced polydipsia (SIP), a potential model of stress and drug abuse, has been reported to differ between the two strains (see [Pharmacol. Biochem. Behav. 67 (2002) 809]) with F344 rats displaying greater levels of consumption than LEW rats. Given the importance of SIP as a behavioral model of stress and of drug abuse, the present study further explored SIP in F344 and LEW strains by assessing the acquisition and steady-state performance of SIP (under a fixed-time 30 schedule of food delivery; FT30), its characteristic postprandial temporal licking pattern and its modulation by variations in the food delivery schedule (FT15, FT30 and FT60). F344 rats acquired SIP at a faster rate and drank at a higher asymptotic level than LEW rats. Both strains displayed the typical inverted U-shaped post-pellet pattern of drinking and changes in levels of consumption (and displacement of the initiation of post-pellet drinking) with changes in the FT value, supporting the position that the increased drinking seen in both groups was schedule induced. These strain differences in SIP are consistent with the fact that the F344 and LEW strains differ on other behavioral and physiological indices of stress and raise the issue of the use of this model in the assessment of differential drug intake between the two strains.

Animals↗

PubMed2002

Maternal behavior in F344/N and LEW/N rats. Effects on carrageenan-induced inflammatory reactivity and body weight.

Inbred Fischer (F344/N) and Lewis (LEW/N) rats differ on a myriad of behavioral and physiological endpoints, such as inflammatory, startle and drug responsivity. These differences point to underlying genetic differences between the strains. However, genetic models of hypertension have shown the importance of the maternal environment in the development of high blood pressure, suggesting that maternal influences might also play a role in adult phenotypes of the LEW/N and F344/N strains. This was tested in the present series of experiments in which the effects of crossfostering on carrageenan-induced inflammation and on body weight were examined in the two strains. Following the demonstration that the two strains differed in maternal behavior (Experiment 1), which was independent of the pup being reared (Experiment 2), crossfostered and in-fostered pups from the LEW/N and F344/N strains were injected with carrageenan (at 60 days of age) and subsequently assessed for the accumulation of exudate in response to the injection. Body weights were also monitored from birth through 60 days of age. Although crossfostering affected body weight of the two strains, specifically, reducing weights in LEW/N pups reared by F344/N dams and increasing weights of F344/N pups reared by LEW/N dams, crossfostering did not affect inflammatory reactivity to carrageenan. Specifically, LEW/N pups had a greater level of exudate than F344/N pups, independent of the conditions under which they were reared, suggesting that differences in the inflammatory response between these two strains are under a high degree of genetic control. These results were discussed in terms of genetic factors mediating the early form of immune reactivity induced by carrageenan.

Animals↗

PubMed2002

Ethanol preexposure attenuates the interaction of ethanol and cocaine in taste aversion learning.

Although the potentiating effects of ethanol and cocaine have been well documented, little has been reported regarding the effects of ethanol or cocaine history on this interaction. In the present study, female Long-Evans rats received five exposures to ethanol (3.5 g/kg ip) or vehicle prior to taste aversion conditioning in which a novel saccharin solution was paired with either ethanol (0.56 g/kg ip), cocaine (25 mg/kg sc) or the combination (or the drugs' vehicle) for a total of five conditioning trials. Nonpreexposed subjects conditioned with the ethanol/cocaine combination displayed aversions, drinking levels significantly less than nonpreexposed subjects conditioned with either drug alone. Further, the aversions produced by the combination were greater than the sum of the aversions produced by ethanol and cocaine, alone. Ethanol-preexposed animals conditioned with the combination displayed an attenuated aversion, drinking significantly greater amounts of saccharin than nonpreexposed conditioned subjects and not differing from controls. Although the basis for the attenuation by ethanol of the aversions induced by the drug combination is not known, the present findings may have implications for the use and abuse of the combination in that alcohol history may reduce the subsequent toxicity of the combination that in turn may affect its acceptability.

Animals↗

PubMed2002

Asymmetric serial interactions between ethanol and cocaine in taste aversion learning.

Although the interaction between ethanol and cocaine is well documented, it has generally been limited to situations in which the two drugs are given concurrently. Little exists on the interaction between ethanol and cocaine when one drug is given prior to the other. In Experiment 1, female Long-Evans rats were given five exposures to ethanol (2 g/kg ip) or vehicle prior to taste aversion conditioning with cocaine (32 mg/kg sc) for a total of five conditioning trials. In Experiment 2, rats were given five exposures to cocaine (32 mg/kg sc) or vehicle prior to taste aversion conditioning with ethanol (2 g/kg ip) for a total of five conditioning trials. Ethanol-preexposed, cocaine-conditioned animals (Experiment 1) displayed attenuated aversions to the cocaine-associated solution, drinking significantly greater amounts of saccharin than vehicle-preexposed, conditioned subjects. Conversely, cocaine-preexposed, ethanol-conditioned animals (Experiment 2) displayed robust aversions to the ethanol-associated solution, drinking levels comparable to those consumed by vehicle-preexposed, conditioned subjects and drinking significantly less than controls. Although the basis for these asymmetric effects is not known, they may have implications for abuse vulnerability in that drug history may impact subsequent drug toxicity that, in turn, may alter drug acceptability.

Animals↗

PubMed2002

Modulation of cocaine-induced place preferences by alcohol.

Behavioral and physiological evidence suggests that alcohol modulates the effects produced by cocaine. To assess whether such modulation is evident with cocaine's affective properties, the present studies examined the effects of alcohol on cocaine-induced conditioned place preferences (CPP). In Experiment 1, male Sprague-Dawley rats were assigned to one of three groups based on whether they were conditioned with 20 mg/kg cocaine (Group C), 0.5 g/kg alcohol (Group A), or the combination (Group C/A). On the first conditioning trial, animals were injected with the drug(s) or vehicle and placed on one side of a place preference apparatus. On the next day, animals initially injected with drug received vehicle (and vice versa) and placed on the other side of the chamber. This cycle was repeated four times. Animals were then tested for their compartment preference. In Experiment 2, subjects were treated identically except that 1.5 g/kg alcohol was administered. In both experiments, Group C displayed a significant preference for the drug-paired compartment. Group A (in both experiments) showed no conditioned effect. In Experiment 1, Group C/A failed to display a significant preference, spending an amount of time in each compartment that was the numerical average of Groups C and A. In Experiment 2, the cocaine-induced preference was completely abated by 1.5 g/kg alcohol. These results indicate that alcohol produces a dose-dependent modulation of the affective properties of cocaine.

Animals↗

PubMedDate not supplied

Effects of alcohol on cocaine lethality in rats: acute and chronic assessments.

Cocaine and alcohol is a popular, yet toxic, drug combination that results in effects greater than that of either drug alone. The following experiment presents additional evidence that supports this position. Specifically, the lethal effects of acute (1 day) and chronic (4 days) alcohol (0.5 g/kg), cocaine (20, 30, or 40 mg/kg), or the respective alcohol/cocaine combinations were assessed in rats. For acute drug administration, lethality was only evident in those animals administered the combination of 0.5 g/kg alcohol and 40 mg/kg cocaine, supporting the position that the effects of combining alcohol and cocaine are greater than either drug alone. Chronic drug administration resulted in a weak sensitization to cocaine-induced lethality that was increased when alcohol was combined with cocaine. Together, this evidence suggests that combining alcohol and cocaine (acutely) can have lethal consequences in rats that are greater than either drug alone, effects that can be exacerbated with chronic use.

Animals↗