Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Nov 2000
Pharmacological identification of SM-21, the novel sigma(2) antagonist.
SM-21 is a tropane analogue with high affinity and selectivity for sigma(2) receptor subtype. In the absence of highly selective sigma(2) antagonists, the aim of the present study was to determine whether SM-21 is endowed with antagonistic activity. ⋯ SM-21 (10 nmol/0.5 microl) was able to prevent torsion of the neck obtained by administration of the sigma(1)-sigma(2) agonist 1,3-di-(2-tolyl)guanidine (DTG, 5 nmol/0.5 microl) in the red nucleus. These data indicate that SM-21 is a potent and selective sigma(2) antagonist.
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Pharmacol. Biochem. Behav. · Nov 2000
Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats.
Performance on working memory tasks, a measure of prefrontal cortical function, is impaired by exposure to mild stress as well as the anxiogenic drug, FG7142. Previous studies have shown that like stress, FG7142 increases catecholamine release in the prefrontal cortex (PFC) and that high levels of dopamine (DA) D(1) and norepinephrine (NE) alpha-1 receptor stimulation underlie the FG7142-induced cognitive impairment. Both the FG7142-induced DA turnover and working memory deficit can be blocked by pretreatment with the nonselective NE alpha-2/imidazoline I1 receptor agonist, clonidine. ⋯ Neither clonidine nor guanfacine had any effect on performance when administered alone. This study suggests that stimulation of the NE alpha-2A receptor subtype is sufficient to ameliorate the cognitive deficit induced by FG7142. Clonidine's sedative and hypotensive side effects limit its therapeutic usefulness; however, selective alpha-2A receptor agonists may be effective in treating prefrontal cognitive deficits in stress-related neuropsychiatric disorders with fewer side effects.
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Pharmacol. Biochem. Behav. · Jun 2000
Multiple ejaculations and chronic fluoxetine: effects on male rat copulatory behavior.
Male rats were treated with fluoxetine (FLX) or vehicle daily for 14 days and copulatory behavior tested on day 15. Rats were either mated to three ejaculations or to sexual exhaustion. Both standard measures and the mount bout analysis were used to evaluate the effects of the chronic FLX on male rat copulatory behavior. ⋯ Analysis of the last three ejaculations in those animals that mated to exhaustion did not reveal an effect of FLX. The behavioral pattern of FLX-treated animals during the first three ejaculations resembled that observed during the last three ejaculatory series in the vehicle-treated animals that mated to exhaustion. The results are discussed in terms of the serotonergic effects on male rat sexual behavior.
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Pharmacol. Biochem. Behav. · Apr 2000
Decreased accumbens dopamine release after cocaine challenge in behaviorally sensitized female rats.
The effects of the competitive NMDA receptor antagonist CPP on the initiation of behavioral sensitization to acute cocaine and basal and acute cocaine-induced dopamine (DA) release in the nucleus accumbens (NAC) were assessed in female Sprague-Dawley rats. Cocaine pretreated rats (30 mg/kg IP, once daily for 7 days) challenged with cocaine (10 mg/kg) on day 8 displayed increased motor activity relative to controls challenged with cocaine on day 8. ⋯ Acute cocaine challenge on day 8 resulted in increased extracellular DA concentrations in the NAC in control rats, no increase in rats pretreated with CPP plus cocaine, and a decrease in rats pretreated with cocaine only. These data demonstrate that development of behavioral sensitization to cocaine in female Sprague-Dawley rats can be completely blocked by a peripherally administered competitive NMDA receptor antagonist and that an increase in DA release in the NAC after a cocaine challenge is not an absolute requirement for expression of motor sensitization to cocaine in female rats.
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Pharmacol. Biochem. Behav. · Nov 1999
Peptide immunoreactivity in aged rat cortex and hippocampus as a function of memory and BDNF infusion.
Brain-derived neurotrophic factor (BDNF) modulates neuropeptide levels in hippocampus and cortex of young adult rats. Neuropeptide levels are altered in some age-related disorders, such as Alzheimer's and Parkinson's Disease. BDNF may be able to rectify peptide abnormalities but, because plasticity decreases with age, BDNF may not alter peptide levels as readily in aged animals. ⋯ Results showed that BDNF upregulated cortical NPY-immunoreactivity (ir) and SOM-ir, upregulated hippocampal NPY-ir, and downregulated hippocampal DYN-ir in both aged and young rats. In addition, BDNF significantly and selectively normalized the areas of atrophied deep cortical CCK-ir cell profiles in aged-impaired rats. Finally, decreased CCK-ir fiber density was found in the hippocampal formation of aged memory-impaired rats.