Biomedical subjects

Linda A Parker

Publications and source records attributed to Linda A Parker.

At least 19 recordsLinked to original sources

PubMed2006

Effect of delta9-tetrahydrocannabinol on quinine palatability and AM251 on sucrose and quinine palatability using the taste reactivity test.

Here we provide evidence that the cannabinoid agonist, Delta9-tetrahydrocannabinol (Delta9-THC) enhances quinine palatability and the CB1 antagonist/inverse agonist, AM251, reduces sucrose and quinine palatability using the taste reactivity test, which provides a direct measure of palatability independently of appetitive behavior. In Experiment 1, rats were treated with a low dose of Delta9-THC (0.5 mg/kg) or Vehicle 30 min, 60 min, 120 min or 240 min prior to a 5-min intraoral infusion of a highly unpalatable 0.05% quinine solution. Regardless of the post-injection interval, Delta9-THC reduced rejection of quinine. The Delta9-THC-induced palatability shift was reversed by AM251. In Experiment 2, rats were injected with either AM251 (1 mg/kg) or Vehicle prior to receiving a 5-min intraoral infusion of either 32% sucrose or 0.05% quinine solution. AM251 significantly decreased sucrose-elicited hedonic reactions across both time intervals; however, AM251 did not significantly modify the rejection of 0.05% quinine solution. When the concentration of the quinine solution was reduced to 0.01% in Experiment 3, AM251 enhanced quinine aversion. Although the range of concentrations of the solutions tested in the present data is limited, our results suggest that the cannabinoid system may modulate the palatability of ingested substances regardless of the palatability of the ingested substance.

Animals↗

PubMed2006

Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat.

RATIONALE: The endogenous cannabinoid system plays a vital role in the control of nausea and emesis. Because of the rapid breakdown and hydrolysis of endocannabinoids, such as anandamide, the therapeutic effects may be enhanced by prolonging their duration of action. OBJECTIVE: The present experiment evaluated the potential of various doses of URB597, a fatty acid amide hydrolase (FAAH) inhibitor, alone and in combination with systemic administration of anandamide to modulate the establishment of lithium-induced conditioned taste reactivity responses in rats. MATERIALS AND METHODS: In experiment 1, on the conditioning day, rats first received an injection of 0.3 mg/kg URB597, 0.15 mg/kg URB597, or vehicle and then received a second injection of anandamide (5 mg/kg) or vehicle, before a 3-min exposure of 0.1% saccharin by intraoral infusion. Immediately after the saccharin exposure, the rats were injected with lithium chloride. On each of three test days, rats received a 3-min intraoral infusion of saccharin solution, and the taste reactivity responses were videotaped and monitored. In experiment 2, the effects of pretreatment with the CB(1) antagonist, AM-251, on URB597 and anandamide-induced suppressed aversion was evaluated. RESULTS: Administration of URB597 alone and in combination with anandamide reduced active rejection reactions elicited by a LiCl-paired saccharin solution; both effects were reversed by pretreatment with AM-251, suggesting that they were CB(1) receptor mediated. CONCLUSIONS: The results suggest that prolonging the action of anandamide by pretreatment with the FAAH inhibitor, URB597, suppresses lithium-induced nausea in the rat.

Amidohydrolases↗

PubMed2006

Conditioned gaping in rats: a selective measure of nausea.

When intraorally infused with a flavored solution previously paired with an emetic drug, rats display a characteristic gaping reaction that reflects conditioned nausea in this species that is unable to vomit. The commonly used conditioned taste avoidance measure, is not a selective measure of nausea because nearly every drug tested (even rewarding drugs) is capable of producing a conditioned taste avoidance. In contrast, only emetic drugs produce conditioned gaping reactions in rats, and anti-emetic drugs interfere with the establishment and the expression of conditioned gaping reactions but do not interfere with conditioned taste avoidance. The conditioned gaping reaction can be used as a pre-clinical tool to evaluate the side effects of nausea that might result from newly developed pharmaceutical agents.

Animals↗

PubMed2006

Exposure to a lithium-paired context elicits gaping in rats: A model of anticipatory nausea.

Chemotherapy patients report anticipatory nausea and vomiting upon re-exposure to the cues previously associated with the treatment. Although rats do not vomit, they display a distinctive gaping reaction when exposed to a toxin-paired flavored solution. Here we report that rats also display gaping reactions during exposure to a context previously paired with the illness-inducing effects of lithium chloride (Experiment 1). This gaping reaction is suppressed by pretreatment with the antiemetic agent, Delta 9-tetrahydrocannabinol, but not ondansetron (Experiment 2). The finding that gaping is elicited by an illness-paired context confirms the proposal that an illness-paired context can evoke a conditioned state of nausea and supports the case of context-aversion as a rat model for anticipatory nausea.

Animals↗

PubMed2006

Renewal effect: context-dependent extinction of a cocaine- and a morphine-induced conditioned floor preference.

RATIONALE: Extinction of fear conditioning has been demonstrated to be context dependent. The experiments in this study evaluate whether extinction of a drug-cue association is also context dependent, using a conditioned floor preference procedure. METHODS: A drug (cocaine or morphine)-floor association was established in a specific context (black or white box). Rats were then given extinction training in which they were exposed to the floors in the conditioning context (Same) or in a different context (Diff) in the absence of the drug. In experiments 1 and 2, during drug-free extinction training, rats were confined to the drug-paired floor on 1 day and the saline-paired floor on the next day over extinction trials. In experiment 3, during drug-free extinction training, rats were given a choice between the drug-paired floor and the saline-paired floor over extinction trials. In all experiments, rats were then returned to the original conditioning context and tested for floor preference. RESULT: Extinction of both the cocaine- and morphine-induced floor preference was greater when the rats received extinction training in the same context as conditioning than when they received extinction training in a different context. CONCLUSION: Extinction of associations between external stimuli and the rewarding properties of a drug is context dependent, suggesting that extinction treatments would be most beneficial if conducted in the context in which the original association was established.

Animals↗

PubMed2006

The role of nausea in taste avoidance learning in rats and shrews.

When paired with a novel flavoured solution, the injection of an emetic drug, such as lithium chloride, produces avoidance of that solution in both non-emetic rats and in emetic shrews. On the other hand, the pairing of a novel flavour with a drug with rewarding properties results in conditioned taste avoidance in rats, but in conditioned taste preference in shrews. It, therefore, appears that nausea may be necessary for the establishment of conditioned taste avoidance in the emetic shrew, but not in the non-emetic rat. Indeed, pre-treatment with the anti-emetic agents, ondansetron or Delta9-tetrahydrocannabinol, interferes with the establishment of lithium-induced conditioned taste avoidance in the shrew, but does not even attenuate the establishment of lithium-induced conditioned taste avoidance in the rat. The results of a number of studies suggest that the nature of flavour-drug associations varies on the basis of the emetic capacity of the species.

Animals↗

PubMed2006

Artificial rearing alters the response of rats to natural and drug-mediated rewards.

Artificial rearing (AR) of infant rats permits precise control over key features of the early environment without maternal influence. The present study examined the behavioral response of AR rats towards natural and drug-mediated rewards, as well as their exploratory and affective behaviors. Adolescent AR rats showed increased preference for sucrose consumption relative to chow and demonstrated greater activity in the open field and in the elevated plus-maze compared to maternally reared (MR) rats. With respect to measures of emotionality, AR rats showed enhanced avoidance of the open arms of the plus-maze, indicating increased anxiety, but they did not differ from MR rats in exploring the center of the open field. Adult AR rats displayed a stronger conditioned response to morphine in a place preference test. These findings support the potential of the AR model to contribute to understanding the role of early experience in the development of behavioral motivation.

Affect↗

PubMed2006

Chronic treatment with Delta-9-tetrahydrocannabinol alters the structure of neurons in the nucleus accumbens shell and medial prefrontal cortex of rats.

The potential of repeated exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC) to produce long-lasting changes in synaptic connections in a manner similar to other drugs of abuse was evaluated in Sprague-Dawley rats. For 12 days, rats received two i.p. injections per day (8 h apart) of vehicle, a low dose of Delta(9)-THC (0.5 mg/kg), or escalating doses of Delta(9)-THC (0.5-4.0 mg/kg). Thirty days later, they were evaluated for sensitized locomotor activity (during the night cycle) for 60 min on each of three trials. Using a within-groups design, rats were tested following an injection of vehicle, 0.5 mg/kg Delta(9)-THC or 2.0 mg/kg Delta(9)-THC. The rats showed no evidence of sensitized locomotor activity in any group. Twenty-four hours after the final sensitization test, their brains were removed and then processed for Golgi-Cox staining. Prior exposure to Delta(9)-THC (both the low dose and the escalating doses) increased the length of the dendrites as well as the number of dendritic branches in the shell of the nucleus accumbens and in the medial prefrontal cortex, but not in the hippocampus, striatum, orbital frontal cortex, parietal cortex, or occipital cortex. These results are similar to those evident in brains of rats sensitized to amphetamine, and support previous findings that cannabinoids promote DA activity in the mesolimbic DA system.

Animals↗

PubMed2006

Effect of conditioning method and testing method on strength of lithium-induced taste aversion learning.

Here the authors evaluated the effect of the method of conditioning (bottle or intraoral [IO] infusion) on the strength of a flavor-drug association when measured in a standard 1-bottle consumption test or when measured by IO infusion in a taste reactivity test. When tested with the bottle test in Experiment 1, rats conditioned by bottle displayed stronger taste avoidance than those conditioned by IO infusion. When tested for rejection reactions with the taste reactivity test in Experiment 2, rats conditioned by infusion displayed a stronger aversion than did rats conditioned by bottle. The results suggest that when the contextual cues of conditioning are similar at conditioning and testing, a stronger association is evident regardless of the individual specifics of each method. These results may shed light on recent reports that different neural mechanisms are involved in conditioning by active consumption and passive infusion.

Analysis of Variance↗

PubMed2006

Extinction of a saccharin-lithium association: assessment by consumption and taste reactivity.

Extinction of a conditioned palatability shift preceded extinction of conditioned taste avoidance whether rats were tested using a within-subjects design or a between-subjects design. In each of two experiments, consumption of 0.1% saccharin was paired with either 20 ml/kg of 0.15 M LiCl or equi-volume physiological saline on a single trial. In Experiment 1, on each of 10 extinction trials, rats were given a taste reactivity test immediately prior to a consumption test. In Experiment 2, half of the rats were extinguished by taste reactivity testing and half of the rats were extinguished by a consumption test on each of 10 extinction trials. In both experiments, the aversive reactions of gaping and passive dripping were extinguished in a single trial and the suppression of ingestive reactions was extinguished in 2 trials; however, extinction of taste avoidance required 4-5 trials. These results suggest that rats continue to avoid a lithium-paired flavor even when they do not have an aversion to the taste.

Animals↗

PubMed2005

Delta-9-tetrahydrocannabinol and cannabidiol, but not ondansetron, interfere with conditioned retching reactions elicited by a lithium-paired context in Suncus murinus: An animal model of anticipatory nausea and vomiting.

Chemotherapy patients report not only acute nausea and vomiting during the treatment itself, but also report anticipatory nausea and vomiting upon re-exposure to the cues associated with the treatment. We present a model of anticipatory nausea based on the emetic reactions of the Suncus murinus (musk shrew). Following three pairings of a novel distinctive contextual cue with the emetic effects of an injection of lithium chloride, the context acquired the potential to elicit conditioned retching in the absence of the toxin. The expression of this conditioned retching reaction was completely suppressed by pretreatment with each of the principal cannabinoids found in marijuana, Delta(9)-tetrahydrocannabinol or cannabidiol, at a dose that did not suppress general activity. On the other hand, pretreatment with a dose of ondansetron (a 5-HT(3) antagonist) that interferes with acute vomiting in this species, did not suppress the expression of conditioned retching during re-exposure to the lithium-paired context. These results support anecdotal claims that marijuana, but not ondansetron, may suppress the expression of anticipatory nausea.

Analysis of Variance↗

PubMed2005

Effect of Delta9-tetrahydrocannabinol on sucrose palatability as measured by the taste reactivity test.

The taste reactivity test was employed to determine the effect of pre-treatment with Delta9-Tetrahyrdrocannabinol THC on sucrose palatability. In Experiment 1, on each of 9 trials, rats were injected with THC or Vehicle prior to receiving a 5 min intraoral infusion of sucrose solution. The concentration of sucrose (2%, 10% or 32%) and the interval between the injection and the sucrose infusion (30, 60 or 120 min) were varied in a within-subjects design. THC enhanced the frequency of ingestion reactions only when administered 120 min prior to the taste reactivity test, regardless of sucrose concentration. In Experiment 2, the CB1 antagonist, SR141716, reversed the enhanced sucrose palatability produced by THC. These results suggest that the increased intake of palatable food 2 h, but not earlier, following administration of a low dose of THC may be the result of enhanced palatability and that this effect is the result of action of THC at the CB1 receptor.

Animals↗

PubMed2005

Ondansetron and Delta-9-tetrahydrocannabinol interfere with the establishment of lithium-induced conditioned taste avoidance in the house musk shrew (Suncus murinus).

Considerable evidence suggests that rats can learn to avoid a taste in the absence of nausea. The current experiments evaluated the potential of the antiemetic agents, ondansetron (OND) and delta-9-tetrahydrocannabinol (THC), to interfere with lithium chloride (LiCl)-induced taste avoidance in the house musk shrew, Suncus murinus, an insectivore that, unlike rats, is capable of vomiting. At a dose that did not modify saccharin (Experiment 1) or sucrose (Experiment 2) intake, OND prevented the establishment of LiCl-induced taste avoidance in the shrew. A low dose of THC (1 mg/kg), which did not modify sucrose intake during conditioning, also prevented the establishment of LiCl-induced taste avoidance in the shrew. Higher doses of THC were also effective, but they also suppressed sucrose consumption during conditioning. These results suggest that nausea is a necessary component of the unconditioned stimulus for the establishment of conditioned taste avoidance in the shrew, unlike the rat, which does not vomit when injected with a toxin.

Analgesics, Non-Narcotic↗

PubMed2004

A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew).

RATIONALE: The 5-HT3 antagonist, ondansetron (OND), and the cannabinoid, delta9-tetrahydrocannabinol (delta9-THC), have been shown to interfere with emesis; however, their relative and/or combined effectiveness in suppressing vomiting produced by the chemotherapeutic agent, cisplatin, is unknown. OBJECTIVE: To evaluate the potential of: 1) a broad range of doses of delta9-THC and OND to prevent cisplatin-induced vomiting and retching in the Suncus murinus (house musk shrew), 2) combined treatment with ineffective individual doses of delta9-THC and OND to prevent cisplatin-induced vomiting and retching, 3) the CB1 receptor antagonist, SR141716, to reverse the antiemetic effects of OND, and 4) cannabidiol (CBD), the principal non-psychoactive component of marijuana, to reverse cisplatin-induced vomiting in the shrew. METHODS: Shrews were injected with various doses of OND (0.02-6.0 mg/kg), delta9-THC (1.25-10 mg/kg) and a combination of ineffective doses of each (0.02 mg/kg OND+1.25 mg/kg delta9-THC) prior to being injected with cisplatin (20 mg/kg) which induces vomiting. Shrews were also injected with CBD (5 mg/kg and 40 mg/kg) prior to an injection of cisplatin. RESULTS: OND and delta9-THC both dose-dependently suppressed cisplatin-induced vomiting and retching. Furthermore, a combined pretreatment of doses of the two drugs that were ineffective alone completely suppressed vomiting and retching. CBD produced a biphasic effect, suppressing vomiting at 5 mg/kg and potentiating it at 40 mg/kg. CONCLUSIONS: A low dose of the non-intoxicating cannabinoid CBD may be an effective anti-emetic treatment and combined doses of OND and delta9-THC that are ineffective alone suppresses cisplatin-induced emetic reactions in shrews.

Animals↗

PubMed2004

Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats.

RATIONALE: Using the place-preference conditioning paradigm, we evaluated the potential of the two most prominent cannabinoids found in marijuana, the psychoactive component delta9-tetrahydrocannabinol (delta9-THC) and the nonpsychoactive component cannabidiol (CBD), to potentiate extinction of a cocaine-induced and an amphetamine-induced conditioned place preference in rats. METHODS: To determine the effects of pretreatment with delta9-THC or CBD on extinction, a cocaine-induced and amphetamine-induced place preference was first established. Rats were then given an extinction trial, during which they were confined to the treatment-paired floor for 15 min. Thirty minutes prior to the extinction trial, they were injected with a low dose of delta9-THC (0.5 mg/kg), CBD (5 mg/kg) or vehicle. The potential of the CB1 receptor antagonist, SR141716, to reverse the effects of delta9-THC or CBD was also evaluated. To determine the hedonic effects of CBD, one distinctive floor was paired with CBD (5 mg/kg) and another with saline. Finally, to determine the effect of delta9-THC.or CBD on the establishment and/or the expression of a place preference during four cycles of conditioning trials, rats were injected with delta9-THC (0.25-1 mg/kg), CBD (5 mg/kg) or vehicle 25 min prior to receiving an injection of amphetamine followed by placement on the treatment floor; on alternate days, they received injections of vehicle followed by saline and placement on the nontreatment floor. The rats then received two test trials; on one trial they were pretreated with the cannabinoid and on the other trial with vehicle. RESULTS: delta9-THC and CBD potentiated the extinction of both cocaine-induced and amphetamine-induced conditioned place preference learning, and this effect was not reversed by SR141716. The cannabinoids did not affect learning or retrieval, and CBD was not hedonic on its own. CONCLUSIONS: These results are the first to show that both delta9-THC, which acts on both CB 1 and CB2 receptors, and CBD, which does not bind to CB1 or CB2 receptors, potentiate the extinction of conditioned incentive learning.

Amphetamine↗

PubMed2004

5,7-dihydroxytryptamine lesions of the dorsal and median raphe nuclei interfere with lithium-induced conditioned gaping, but not conditioned taste avoidance, in rats.

Both the dorsal and median raphe nuclei of the midline brainstem region in rats were lesioned with the neurotoxin 5,7-dihydroxytryptamine. Rats were then surgically implanted with intraoral cannulas for fluid delivery and received a single conditioning trial in which 2-min saccharin infusion was followed by either lithium or saline administration. The conditioned gaping seen in the lithium-conditioned rats was significantly attenuated by raphe lesions, indicating that reduction of forebrain serotonin levels interferes with conditioned gaping. However, lesioned rats still expressed comparable conditioned taste avoidance as measured by both the 1- and 2-bottle consumption tests. These results parallel previous pharmacological findings indicating that reduction of serotonin activity interferes with conditioned gaping, but not conditioned taste avoidance.

5,7-Dihydroxytryptamine↗

PubMed2003

Effect of cannabinoids on lithium-induced vomiting in the Suncus murinus (house musk shrew).

RATIONALE: Marijuana has been reported to interfere with nausea and vomiting in chemotherapy patients. The principal cannabinoids found in marijuana include the psychoactive compound Delta-9-tetrahydrocannabinol (THC) and the non-psychoactive compound cannabidiol (CBD). The experiments reported here evaluated the potential of THC and CBD to interfere with vomiting in the Suncus murinus (house musk shrew) produced by lithium chloride (LiCl), which is the most commonly employed unconditioned stimulus for taste avoidance. OBJECTIVES: To evaluate the potential of the principal components of marijuana, THC and CBD, to suppress Li-induced vomiting in the house musk shrew. METHODS: Shrews were injected with vehicle or one of two cannabinoids [Delta-9-THC (1-20 mg/kg), or CBD (2.5-40 mg/kg)] 10 min prior to an injection of LiCl (390 mg/kg of 0.15 M) and were then observed for 45 min. The frequency of vomiting episodes and the latency to the first episode were measured. The role of the CB1 receptor in these effects was also evaluated by pretreatment with SR-141716. RESULTS: Delta-9-THC produced a dose-dependent suppression of Li-induced vomiting, with higher doses producing greater suppression than lower doses. CBD produced a biphasic effect with lower doses producing suppression and higher doses producing enhancement of Li-induced vomiting. The suppression of Li-induced vomiting by THC, but not by CBD, was reversed by SR-141716. CONCLUSIONS: These results indicate that two major cannabinoid compounds found in marijuana, THC and CBD, are effective treatments for Li-induced vomiting; however, only THC acts by the CB1 receptor. The effects of THC and CBD on vomiting were dose dependent; with THC the effect was linear, but with CBD the effect was biphasic.

Animals↗

PubMed2003

The 5-HT1A agonist 8-OH-DPAT dose-dependently interferes with the establishment and the expression of lithium-induced conditioned rejection reactions in rats.

RATIONALE: The present experiments evaluated the potential of the 5-HT(1A )agonist, 8-OH-DPAT (DPAT), which reduces serotonin availability, to interfere with both the establishment and with the expression of lithium-induced conditioned rejection reactions (experiment 1) and lithium-induced taste avoidance (experiment 2). OBJECTIVES. To determine the effect of reduced serotonin availability on conditioned rejection reactions, a rat model of nausea. METHODS: Rats were injected with 8-OH-DPAT [at doses of 0.0 (saline), 0.01 or 0.1 mg/kg, SC] 30 min prior to exposure to 0.1% saccharin solution by intra-oral infusion (experiment 1) or by bottle presentation (experiment 2). Immediately following saccharin exposure, rats were injected with 20 ml/kg lithium chloride (0.15 M) or 20 ml/kg saline solution. On each of three test trials, rats were injected with DPAT [0.0 (saline), 0.01 and 0.1 mg/kg, SC; counterbalanced order], 30 min prior to exposure to saccharin solution by intra-oral infusion (experiment 1) or by a two-bottle test (experiment 2: saccharin and water). RESULTS: DPAT interfered with both the establishment (at a dose of 0.1 mg/kg, SC) and with the expression (at doses of 0.01 and 0.1 mg/kg, SC) of lithium-induced conditioned rejection reactions; however, DPAT did not modulate taste avoidance in a consumption test. CONCLUSIONS: These results indicate that conditioned rejection reactions, but not taste avoidance, can be attenuated by the anti-emetic agent, 8-OH-DPAT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗