Chronic desipramine enhances the effect of locally applied amphetamine on interstitial concentrations of dopamine in the nucleus accumbens.

In vivo microdialysis was used to study the effect of chronic desipramine (DMI, 5 mg/kg, twice daily for 21 days) on increases in interstitial dopamine (DA) produced by local administration of d-amphetamine (1.0, 3.3 and 10.0 microM) in the nucleus accumbens. Locally applied amphetamine increased interstitial DA in a dose-dependent manner. The amphetamine-induced increase was significantly greater in the DMI treated animals. These data suggest that chronic DMI may directly influence the functional status of the DA terminals in the nucleus accumbens.     

Transcatheter arterial embolisation in nasopharyngeal angiofibroma.

Transcatheter arterial embolisation using gelfoam particles has been used in 4 young male patients with nasopharyngeal angiofibroma. The procedure proved to be extremely useful preoperatively in controlling and limiting profuse bleeding during surgery, allowing total excision of the tumor.     

A single dose of meropenem is superior to ciprofloxacin in preventing infections after transrectal ultrasound-guided prostate biopsies in the era of quinolone resistance

Purpose

To evaluate the efficacy of meropenem single dose before transrectal prostate biopsy, instead of ciprofloxacin in the era of fluoroquinolones resistance.

Methods

This prospective study included patients with indications for prostatic biopsy from January to December 2014. Those with known resistance in fluoroquinolones or meropenem or with decreased creatinine clearance were excluded. Patients were randomized into two groups, and statistical analysis was carried out. Group A received a 3-day course of ciprofloxacin 500 bid per os starting the day before biopsy. Group B received 1 g meropenem intravenously 1 h prior to the procedure. Patients were followed up for 15 days, and those with lower urinary tract symptoms (LUTS) and fever were called for hospitalization. Urine and blood cultures were obtained.

Results

A total of 110 patients, 52–75 years old (mean 67.5, median 66) participated in the study, allocated in Groups A and B. After the procedure, 18 patients (32.7 %) of Group A reported macroscopic hematuria, while 10 (18.2 %) reported rectal blood loss. Nine patients (16.3 %) presented because of fever and LUTS. One of them developed septic shock and died in the ICU. Cultures revealed multi-resistant E. coli with high sensitivity to meropenem, and patients were treated accordingly. In Group B, 20 (36.3 %) patients presented with macroscopic hematuria and 9 (16.3 %) with rectal blood loss. One patient returned to hospital with LUTS and fever. Cultures revealed Klebsiella pneumoniae sensitive to colimycine.

Conclusions

A single dose of meropenem prior to prostate biopsy is a safe and effective way to avoid the possible infectious complications in high-risk patients.

     

CB<Subscript>1</Subscript> cannabinoid receptor agonists increase intracranial self-stimulation thresholds in the rat

Rationale Addictive drugs have a number of commonalities in animal behavioral models. They lower intracranial self-stimulation (ICSS) thresholds, support self-administration, and produce conditioned place preference (CPP). However, cannabinoids appear atypical as drugs of abuse, since there are controversial data in the literature concerning their reinforcing properties.Objectives The aim of the present study was to examine the effects of cannabinoids on brain reward using the rate–frequency curve shift paradigm of ICSS.Methods Male Sprague–Dawley rats were implanted with electrodes into the medial forebrain bundle (MFB). Rate–frequency functions were determined by logarithmically decreasing the number of cathodal pulses in a stimulation train from a value that sustained maximal responding to one that did not sustain responding. After brain stimulation reward thresholds stabilized rats received intraperitoneal (IP) injections of the potent CB₁ receptor agonists WIN 55,212-2 (graded doses 0.1, 0.3, 1 and 3 mg/kg), CP 55,940 (graded doses 10, 30, 56 and 100 g/kg), or HU-210 (graded doses 10, 30, 100 g/kg).Results With the exception of the highest dose of all cannabinoid agonists tested, which significantly increased the threshold frequency required for MFB ICSS, all other doses of the tested drugs did not affect ICSS thresholds. The CB₁ receptor antagonist SR141716A reversed the actions of WIN 55,212-2 and CP 55,940, but not HU-210. However, the selective CB₁ cannabinoid receptor antagonist AM 251 counteracted the effect of HU-210. Both CB₁ receptor antagonists, at the doses used in the present study, did not affect reward thresholds by themselves.Conclusions The present results indicate that cannabinoid agonists do not exhibit reinforcing properties in the ICSS paradigm, but rather have an inhibitory influence on reward mechanisms. The results suggest that the anhedonic effects of cannabinoids are probably mediated by cannabinoid CB₁ receptors.     

Acute exposure to a novel object during consolidation enhances cognition

Environmental enrichment enhances learning and memory in both rodents and man. We examined the effect of active manipulation of a novel object (toy) on cognitive performance and acetylcholine (ACh) efflux in the hippocampus of rats. Animals exposed to the toy showed a significant increase in hippocampal ACh efflux provided that they actively manipulated the object. Similarly, a single 1 h introduction of the novel object (toy) immediately after a training session in a radial arm maze significantly improved memory only if the animals actively manipulated the object. The data suggest that environmental enrichment during a critical period (consolidation) is sufficient to improve learning and memory. This effect is likely mediated through an enhancement of hippocampal cholinergic neurotransmission.     

CB1 receptor antagonism increases hippocampal acetylcholine release: site and mechanism of action

Evidence indicates that blockade of cannabinoid receptors increases acetylcholine (ACh) release in brain cortical regions. Although it is assumed that this type of effect is mediated through CB1 receptor (CB1R) antagonism, several in vitro functional studies recently have suggested non-CB1R involvement. In addition, neither the precise neuroanatomical site nor the exact mechanisms underlying this effect are known. We thoroughly examined these issues using a combination of systemic and local administration of CB1R antagonists, different methods of in vivo microdialysis, CB1R knockout (KO) mice, tissue measurements of ACh, and immunochemistry. First, we showed that systemic injections of the CB1R antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR-141716A) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) dose-dependently increased hippocampal ACh efflux. Likewise, local hippocampal, but not septal, infusions of SR141716A or AM251 increased hippocampal ACh release. It is noteworthy that the stimulatory effects of systemically administered CB1R antagonists on hippocampal ACh release were completely abolished in CB1R KO mice. CB1R KO mice had similar basal but higher stress-enhanced hippocampal ACh levels compared with wild-type controls. It is interesting that dopamine D1 receptor antagonism counteracted the stimulatory effect of CB1R blockade on hippocampal ACh levels. Finally, immunohistochemical methods revealed that a high proportion of CB1R-positive nerve terminals were found in hippocampus and confirmed the colocalization of CB1 receptors with cholinergic and dopaminergic nerve terminals. In conclusion, hippocampal ACh release may specifically be controlled through CB1Rs located on both cholinergic and dopaminergic neuronal projections, and CB1R antagonism increases hippocampal ACh release, probably through both a direct disinhibition of ACh release and an indirect increase in dopaminergic neurotransmission at the D1 receptors.     

The 5-HT1A receptor antagonist (S)-UH-301 decreases dopamine release in the rat nucleus accumbens and striatum

Summary In this study we employed in vivo microdialysis to examine the effects of the selective 5-HT_1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [(S)-UH-301] on extracellular concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens (NAC) and dorsal striatum of awake freely moving rats. Systemic administration of (S)-UH-301 (1.25, 2.5, 5.0mg/kg s.c.) dose-dependently decreased extracellular concentrations of DA, DOPAC and HVA in the NAC. (S)-UH-301 (2.5mg/kg s.c.) also decreased DA, but not DOPAC and HVA, concentrations in the striatum. Infusion of low concentrations (1, 10 M) of (S)-UH-301 into either the NAC or the striatum did not affect DA levels, while only the highest concentration (1,000 M) significantly decreased DA levels in both areas. Similarly, infusion of the selective 5-HT_1A receptor agonist (R)-8-hydroxy-2-(di-n-propylamino)tetralin [(R)-S-OH-DPAT] only in high concentrations (100, 1,000 M) decreased DA levels in both regions. These data suggest that (S)-UH-301 decreases DA release both in the NAC and the striatum probably indirectly via its purported DA-D₂/D₃ receptor agonistic properties. However, the observed inhibitory effect of (S)-UH-301 on DA release in the studied brain regions may also be explained, at least partly, by a serotonergic influence on the DA systems, acting at 5-HT_1A receptor sites located elsewhere in the brain.     

Ritanserin potentiates the stimulatory effects of raclopride on neuronal activity and dopamine release selectively in the mesolimbic dopaminergic system

The atypical profile of clozapine and some other new atypical antipsychotic drugs has been attributed to a relatively selective effect on the mesolimbic dopaminergic system, as well as to their potent serotonin 5-HT₂ receptor antagonism and high ratio of 5-HT₂ to dopamine D₂ receptor affinities. It is unclear, however, how concurrent 5-HT₂ and D₂ receptor antagonism specifically affects the mesoaccumbens and the mesocortical dopaminergic systems.The present study examined the effect of pretreatment with the 5-HT₂ receptor antagonist, ritanserin, on changes in midbrain dopamine neuronal activity as well as in forebrain, extracellular concentrations of dopamine, induced by relatively low doses of the D₂ receptor antagonist raclopride, utilizing in vivo extracellular single cell recording techniques and voltammetry in anesthetized rats, as well as microdialysis in freely moving rats. Raclopride alone (10–2560 g/kg, i.v.) induced a dose-dependent increase in three parameters of neuronal activity, i.e. burst firing, firing rate and variation coefficient, of midbrain DA neurons. This effect of raclopride was more pronounced in cells of the ventral tegmental area than in cells of the substantia nigra-zona compacta. Ritanserin alone (1.0 mg/kg, i.v.) also increased all three parameters of neuronal activity in dopamine cells of the ventral tegmental area, but only firing rate in the cells of the substantia nigra. Ritanserin pretreatment (30 min) significantly enhanced the stimulatory effects of low doses of raclopride (10–20 g/kg) on burst firing in dopamine neurons, preferentially in the ventral tegmental area. Raclopride alone (50 g/kg, s.c.) increased extracellular concentrations of dopamine in the medial prefrontal cortex and the dorsolateral striatum by 75 and 110%, respectively, as measured by microdialysis. Ritanserin alone (1.5 mg/kg, s.c.) did not significantly affect cortical and striatal extracellular dopamine concentrations; however, pretreatment (40 min) with ritanserin elevated the raclopride-induced increase of dopamine concentrations in the medial prefrontal cortex to about 250%, but failed to affect the action of raclopride on striatal dopamine levels. Raclopride alone (10 and 320 g/kg, i.v.) dose-dependently increased extracellular concentrations of dopamine in the nucleus accumbens and the dorsolateral striatum to about 500%, as determined by voltammetry. Ritanserin alone (1.0 mg/kg, i.v.) did not significantly affect the voltammetric dopamine signal in the nucleus accumbens or the dorsolateral striatum; however, ritanserin pretreatment (30 min) enhanced the raclopride-induced increase in accumbal but not striatal dopamine concentrations to about 1600%. The stimulatory effect of the combined ritanserin plus raclopride treatment on neuronal activity and DA release was more pronounced in the mesolimbic than the nigrostriatal dopaminergic system.The present data indicate that concurrent 5-HT₂ and D₂ receptor antagonism selectively affects the activity of the mesolimbic dopaminergic system. These findings provide an experimental basis for the notion that combined 5-HT₂ and D₂ receptor antagonism may underlie the limbic mode of action of at least some atypical antipsychotic drugs and consequently contribute to their unique therapeutic effects.