Pharmacology, biochemistry, and behavior
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The recent discovery of arachidonylethanolamide (anandamide), an endogenous ligand for cannabinoid receptors, and the synthesis of SR141716A, a cannabinoid antagonist selective for brain cannabinoid (CB1) receptors, have provided new tools to explore the mechanisms underlying cannabis abuse and dependence. Drug discrimination is the animal model with the most predictive validity and specificity for investigation of the psychoactive effects of cannabinoids related to their abuse potential, because, unlike many other drugs of abuse, delta9-tetrahydrocannabinol (delta9-THC), the major psychoactive ingredient of marijuana, is not self-administered by animals. Results of delta9-THC discrimination studies have revealed that the subjective effects of cannabis intoxication are pharmacologically selective for centrally active cannabinoid compounds, and that cannabis action at CB1 receptors is involved in medication of these effects. ⋯ In contrast, delta9-THC and other structurally diverse cannabinoids fully substitute for delta9-THC at doses that do not substantially affect response rates. Attempts to train animals to discriminate anandamide (or SR141716A) have so far been unsuccessful. Preliminary evidence from drug discrimination studies with more metabolically stable anandamide analogs have suggested that these differences in the discriminative stimulus effects of delta9-THC and anandamide-like cannabinoids are not entirely due to pharmacokinetic factors, but the exact role of "internal bliss" in cannabis intoxication and dependence is still not completely understood.
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Pharmacol. Biochem. Behav. · Apr 1999
Sedation and need-free salt intake in rats treated with clonidine.
The effect of intraperitoneal injection of clonidine (9-72 microg/kg) on need-free 1.5% NaCl intake and on performance (defined as percent of a complete trial) in the rotarod test, was studied in normovolemic adult male rats. Clonidine (18 and 36 microg/kg) inhibited the 1.5% NaCl intake in a 2-h test at doses that did not alter the performance in the rotarod test. ⋯ Sedation was determined either by change in posture (immobility or lack of postural tonus) of the animals during the ingestive test or by their performance in the rotarod test. The results suggest that sedation is not a determinant effect on the inhibition of 1.5% NaCl intake induced by clonidine.
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Pharmacol. Biochem. Behav. · Sep 1998
Chronic running-wheel activity decreases sensitivity to morphine-induced analgesia in male and female rats.
The effects of exercise on morphine-induced analgesia were examined in male and female Long-Evans rats. In Experiment 1, 10 male rats were housed in standard laboratory cages, and 10 in activity wheels for 20 days prior to nociceptive testing. Pain thresholds were assessed using a tail-flick (TF) procedure. ⋯ Experiment 4 investigated whether differences in body weight contributed to the differences in morphine-induced analgesia between chronically active and inactive animals. %MPEs did not vary among male rats maintained at 100, 85, or 77% of their free-feeding body weight. These results indicate that chronic activity can decrease morphine's analgesic properties. These effects may be due to crosstolerance between endogenous opioid peptides released during exercise and exogenous opioids.
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Pharmacol. Biochem. Behav. · Aug 1998
Comparative StudyAnxiolytic-like effects of perospirone, a novel serotonin-2 and dopamine-2 antagonist (SDA)-type antipsychotic agent.
We examined the anxiolytic potential of perospirone, a novel serotonin-2 and dopamine-2 antagonist (SDA)-type antipsychotic agent, and compared its effects with those of the standard anxiolytic diazepam and the conventional antipsychotic haloperidol by using conditioned defensive burying (CDB) and social interaction (SI) tests in rats. The tests were conducted 1 h after oral administration of the drug. Diazepam inhibited CDB specifically directed toward a probe previously associated with brief electric shock and increased the time spent in SI by pairs of naive rats in a brightly illuminated novel environment. ⋯ In contrast, haloperidol failed to inhibit CDB or increase SI. These results suggested that, unlike the conventional antipsychotic haloperidol, perospirone exerts anxiolytic-like effects in animal models with different motivational and emotional states. A braoder efficacy of perospirone for the treatment of anxiety and related symptoms in schizophrenia is discussed.
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Pharmacol. Biochem. Behav. · Jul 1998
Fetal ethanol effects on benzodiazepine sensitivity measured by behavior on the elevated plus-maze.
Rodents prenatally exposed to ethanol demonstrate altered behavioral and hormonal responses to stressful environments. Prenatal ethanol exposure may also have long-term effects on the offspring's GABAergic system. Using the elevated plus-maze, the present study examined the sensitivity of adult Sprague-Dawley rat offspring from prenatal ethanol (E), pair-fed (PF) and ad lib-fed control (C) conditions to the effects of benzodiazepine (BZD) on plus-maze behavior and corticosterone (CORT) responses. ⋯ Further, BZD-treated E males exhibited decreased open and closed arm entries, spent significantly more time in the central area, and had lower CORT levels, another index of fear or stress, compared to BZD-treated PF and C males. These data support and extend previous work demonstrating that the plus-maze provides a reliable measure of anxiety/fear, and that plus-maze behavior is sensitive to anxiolytic agents such as BZD. Furthermore, these data suggest that prenatal ethanol exposure may alter sensitivity to the effects of BZD on plus-maze behavior and CORT responsiveness, and may do so differentially in male and females offspring.