Behavioural pharmacology
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Behavioural pharmacology · Jun 2006
Lowered brain stimulation reward thresholds in rats treated with a combination of caffeine and N-methyl-D-aspartate but not alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate or metabotropic glutamate receptor-5 receptor antagonists.
Previous studies suggested that adenosine A1 and A2A receptor agonists counteract behavioral effects of N-methyl-D-aspartate (NMDA) receptor antagonists while adenosine receptor antagonists may produce opposite effects enhancing the actions of NMDA receptor antagonists. To further evaluate the effects of combined administration of adenosine receptor antagonist caffeine and various NMDA and non-NMDA glutamate receptor antagonists on brain stimulation reward (discrete-trial threshold current intensity titration procedure), rats with electrodes implanted into the ventral tegmental area were tested after pretreatment with NMDA receptor channel blocker MK-801 (0.01-0.3 mg/kg), competitive antagonist D-CPPene (0.3-5.6 mg/kg), glycine site antagonist L-701,324 (1.25-5 mg/kg), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist GYKI-53655 (1-10 mg/kg), metabotropic glutamate receptor 5 (mGluR5) antagonist MPEP (1-10 mg/kg) alone and in combination with caffeine (1-30 mg/kg). MK-801 (0.056 and 0.1 mg/kg) was the only tested glutamate antagonist that lowered self-stimulation thresholds, while D-CPPene (5.6 mg/kg) and MPEP (5.6 and 10 mg/kg) had the opposite effects. ⋯ A low dose of caffeine (3 mg/kg) significantly lowered self-stimulation thresholds only when given together with MK-801 (0.03 mg/kg) or D-CPPene (3 mg/kg). Combined with the same antagonist drugs, higher doses of caffeine (10 and 30 mg/kg) facilitated time-out responding. These results indicate that, within a limited dose range, caffeine in combination with an NMDA receptor channel blocker and a competitive antagonist significantly lowers brain stimulation reward thresholds in rats.
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Behavioural pharmacology · May 2006
Discriminative stimulus effects of flumazenil: perceptual masking by baclofen, and lack of substitution with gamma-hydroxybutyrate and its precursors 1,4-butanediol and gamma-butyrolactone.
Pigeons trained to discriminate 0.1 mg/kg flumazenil, proposed as an in-vivo model to study interactions with diazepam-insensitive gamma-aminobutyric acid (GABA)A receptors, were tested with various GABAergic and non-GABAergic compounds. As a result of its pharmacological selectivity, the model was suitable for further examining previously reported flumazenil-like effects of gamma-hydroxybutyrate (GHB). Flumazenil and the GABAA negative modulator Ro 15-4513 produced 82-100% flumazenil-appropriate responding. ⋯ When CGP35348 was given together with GHB to block its GABAB agonist effects, GHB did not produce flumazenil-appropriate responding. Conceivably, effects of GHB at non-GABAB receptors (e.g. diazepam-sensitive GABAA receptors and GHB receptors) may interfere with the expression of its flumazenil-like discriminative stimulus effects. The asymmetric substitution between GHB and flumazenil is consistent with the hypothesis that the discriminative stimulus effects of GHB consist of several components, not all of which are mimicked by flumazenil.
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Behavioural pharmacology · May 2006
Influence of intracerebroventricular administration of cannabinergic drugs on morphine state-dependent memory in the step-down passive avoidance test.
The effects of cannabinergic drugs on morphine state-dependent memory of passive avoidance task were examined in mice. Pre-training (0.25, 0.5 and 5 mg/kg) and post-training (5 mg/kg) administration of morphine impaired memory retrieval on the test day. Impairment of memory retrieval by morphine (5 mg/kg) on the test day was reversed by pre-test administration of the same dose of the opioid. ⋯ Pre-training administration of WIN55,212-2 (1 microg/mouse) led to state-dependent learning with impaired memory retrieval on the test day as well, which was reversed by pre-test administration of the drug (0.5, 0.75 and 1 microg/mouse) or morphine (1 and 5 mg/kg). Restoration of impairment induced by WIN55,212-2 was decreased by both the opioid receptor antagonists, naloxone (0.01 microg/mouse) and AM251 (20 and 100 ng/mouse). In conclusion, the improvement of memory retrieval by morphine treatment on the test day seems to be induced, at least in part, by the cannabinoid CB1 receptors.
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Behavioural pharmacology · Nov 2005
Chronic imipramine treatment sensitizes 5-HT1A and 5-HT 2 A receptors in the dorsal periaqueductal gray matter: evidence from the elevated T-maze test of anxiety.
The dorsal periaqueductal gray matter (DPAG) has been implicated in the mediation of escape, a defensive behavior associated with panic disorder (PD). Chronic treatment with the anti-panic agent imipramine enhances the inhibitory effect on escape evoked by DPAG electrical stimulation of intra-DPAG administration of the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the preferential 5-HT 2 A receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI). In the present study we further explore the hypothesis that sensitization of 5-HT1A and 5-HT 2 A receptors in the DPAG is involved in the anti-panic effect of imipramine. ⋯ Microinjection of 8-OH-DPAT (3.2 nmoles), but not of DOI, impaired inhibitory avoidance, and this anxiolytic effect did not differ between animals treated with saline or imipramine. Chronic buspirone did not change the effect of 8-OH-DPAT and DOI on inhibitory avoidance and escape. Therefore, chronic imipramine seems to sensitize both 5-HT1A and 5-HT 2 A receptors in the DPAG, strengthening the view that these receptors are involved in the mode of action of anti-panic drugs.
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Behavioural pharmacology · Feb 2004
Comparative StudyAttentional and evaluative biases for smoking cues in nicotine dependence: component processes of biases in visual orienting.
The present study investigated attentional and evaluative biases for smoking-related cues in cigarette smokers and non-smokers. Using a visual probe task, we manipulated the presentation conditions of the stimuli to examine: (1). whether smokers have a bias to allocate attention towards smoking-related pictures that appear below the threshold of conscious awareness; and (2). whether attentional biases for smoking-related pictures that appear above the threshold of awareness operate both in initial orienting and in the maintenance of attention. We also obtained explicit and implicit measures of the valence of the smoking-related pictures from pleasantness ratings and from behavioural responses on a stimulus-response compatibility (SRC) task. ⋯ The bias was not found in a brief (17 ms) masked exposure condition, so there was no evidence that it operated preconsciously. Smokers also showed greater preferences for smoking-related than control cues, compared with non-smokers, on both the explicit and implicit indices of stimulus valence. Results are discussed with reference to incentive and cognitive models of addiction.