NLX-112, a highly selective 5-HT receptor biased agonist, does not exhibit misuse potential in male rats or macaques.

NLX-112 (a.k.a.

Effects of daily Δ-Tetrahydrocannabinol (THC) alone or combined with cannabidiol (CBD) on cognition-based behavior and activity in adolescent nonhuman primates.

Background: Daily use of marijuana is rising in adolescents, along with consumption of high potency marijuana products (high % Δ-9-tetrahydrocannabinol or THC). These dual, related trends have opened gaps in understanding the long-term effects of daily consumption of a high dose of THC in adolescents and whether a therapeutic dose of cannabidiol (CBD) modulates THC effects.

Methods: Adolescent squirrel monkeys (Saimiri boliviensis) were treated daily for four months with vehicle (n = 4), a high THC dose (1 mg/kg i.

"I'm not abusing or anything": patient-physician communication about opioid treatment in chronic pain.

Objective: To characterize clinical communication about opioids through direct analysis of clinic visits and in-depth interviews with patients.

Methods: This was a pilot study of 30 patients with chronic pain, who were audio-recorded in their primary care visits and interviewed after the visit about their pain care and relationship with their physicians. Emergent thematic analysis guided data interpretation.

Analysis of tolerance and behavioral/physical dependence during chronic CB1 agonist treatment: effects of CB1 agonists, antagonists, and noncannabinoid drugs.

Behavioral studies of chronic CB(1) receptor activation may provide a pharmacological approach to understanding efficacy-related differences among CB(1) ligands as well as mechanistic commonalities between cannabinoid and noncannabinoid drugs. In the present studies, the effects of CB(1) agonists [(6aR,10aR)-3-(1-adamantyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol (AM411), 9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol (AM4054), R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate (WIN55,212.2), Δ(9)-tetrahydrocannabinol (Δ(9)-THC), (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide (methanandamide)], CB(1) antagonists [5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (SR141716A), 5-(4-alkylphenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (AM4113)], and dopamine (DA)-related [methamphetamine, (±)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF82958), (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390), (6aR)-5,6,6a,7-tetrahydro-6-propyl-4H-dibenzo[de,g]quinoline-10,11-diol (R-(-)-NPA), haloperidol] and opioid (morphine, naltrexone) drugs on scheduled-controlled responding under a 30-response fixed ratio schedule of stimulus-shock termination in squirrel monkeys were compared before and during chronic treatment with the long-acting CB(1) agonist AM411 (1.

Modification of cocaine self-administration by buspirone (buspar®): potential involvement of D3 and D4 dopamine receptors.

Converging lines of evidence indicate that elevations in synaptic dopamine levels play a pivotal role in the reinforcing effects of cocaine, which are associated with its abuse liability. This evidence has led to the exploration of dopamine receptor blockers as pharmacotherapy for cocaine addiction. While neither D1 nor D2 receptor antagonists have proven effective, medications acting at two other potential targets, D3 and D4 receptors, have yet to be explored for this indication in the clinic.

Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans.

Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts.

Buprenorphine and opioid antagonism, tolerance, and naltrexone-precipitated withdrawal.

The dual antagonist effects of the mixed-action μ-opioid partial agonist/κ-opioid antagonist buprenorphine have not been previously compared in behavioral studies, and it is unknown whether they are comparably modified by chronic exposure. To address this question, the dose-related effects of levorphanol, trans-(-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide (U50,488), heroin, and naltrexone on food-maintained behavior in rhesus monkeys were studied after acute and chronic treatment with buprenorphine (0.3 mg/kg/day).

Discriminative stimulus and reinforcing effects of p-fluoro-L-deprenyl in monkeys.

Rationale: para-Fluoro-L-deprenyl (Fludepryl), a halogenated derivative of L-deprenyl, shares structural similarities with amphetamine and may have potential as a medication for psychostimulant abuse.

Objectives: p-Fluoro-L-deprenyl was evaluated for psychomotor stimulant, discriminative stimulus, and reinforcing effects in squirrel monkeys.

Methods: One group of monkeys was trained under a ten-response fixed-ratio (FR10) schedule of stimulus termination to discriminate between methamphetamine (0.

Drug discrimination in methamphetamine-trained monkeys: effects of monoamine transporter inhibitors.

The involvement of brain monoamine systems in the discriminative stimulus effects of methamphetamine (MA) was studied in squirrel monkeys by evaluating the effects of differentially selective monoamine uptake inhibitors alone and in combination. In monkeys discriminating i.m.

Methamphetamine discrimination and in vivo microdialysis in squirrel monkeys.

Rationale: Characterization of changes in dopamine activity associated with the discriminative-stimulus effects of methamphetamine (MA) and related stimulants will aid our understanding of the role of dopamine in mediating the subjective effects of this drug class.

Objectives: Squirrel monkeys were studied to explore the relationship between discriminative-stimulus effects of psychomotor stimulant drugs and their ability to increase extracellular dopamine levels in the caudate nucleus.

Methods: The ability of MA, cocaine and methylphenidate (0.

Neurologic complications after melarsomine dihydrochloride treatment for Dirofilaria immitis in three dogs.

Melarsomine dihydrochloride is highly effective against both sexes of adult and L5 Dirofilaria immitis. Common adverse reactions include injection site irritation and reluctance to move. Neurologic complications associated with i.

Modification by dopaminergic drugs of choice behavior under concurrent schedules of intravenous saline and food delivery in monkeys.

The allocation of "choice" behavior provides a measure that may be useful in developing experimental models of clinical relapse. In the present experiments, indirect monoaminergic agonists [cocaine, 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR 12909), desipramine, and citalopram], and dopaminergic D1 family agonists [(+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 82958), R-(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (R-(+)-6-BrAPB), and 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 83959)] and D2 family agonists [quinelorane, R-(-)-10,11-dihydroxy-N-n-propylnorapomorphine (R-NPA), (+)-N-propyl-hydroxynaphoxazine [(+)-PHNO], and S-(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol (PD 128907)] were evaluated for their capacity to alter the distribution of choice behavior in cocaine-experienced monkeys. Rhesus monkeys responded on two levers (injection-lever and food-lever) under concurrent fixed ratio 30; fixed ratio 30 schedules of i.

Evaluation of the novel antiepileptic drug, AWD 131-138, for benzodiazepine-like discriminative stimulus and reinforcing effects in squirrel monkeys.

AWD 131-138 [1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one], a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models, was studied in squirrel monkeys trained to discriminate intramuscular (i.m.) injections of midazolam (0.

Long-term survival of dogs with advanced malignant melanoma after DNA vaccination with xenogeneic human tyrosinase: a phase I trial.

Purpose: Canine malignant melanoma (CMM) is a spontaneous, aggressive, and metastatic neoplasm. Preclinical mouse studies have shown that xenogeneic DNA vaccination with genes encoding tyrosinase family members can induce antibody and cytotoxic T-cell responses, resulting in tumor rejection. These studies provided the rationale for a trial of xenogeneic DNA vaccination in CMM using the human tyrosinase gene.

Enadoline discrimination in squirrel monkeys: effects of opioid agonists and antagonists.

Squirrel monkeys were trained to discriminate i.m. injections of the kappa-opioid receptor agonist enadoline (0.

Effect of diazepam on the immune response of rats exposed to acute and chronic swim stress.

To examine the effect of the anti-stress agent diazepam on the immune response, rats were exposed either to acute swim stress, i.e., swimming once only for 30 minutes (non-trained swimmers), or to chronic stress with gradual progressive training for 6 weeks (trained swimmers).

Drug discrimination in methamphetamine-trained monkeys: agonist and antagonist effects of dopaminergic drugs.

The involvement of D1 and D2 subtypes of dopamine receptors in behavioral effects of methamphetamine was studied in squirrel monkeys using a two-lever drug discrimination procedure. In monkeys that discriminated i.m.

JL13, a pyridobenzoxazepine compound with potential atypical antipsychotic activity: a review of its behavioural properties.

The search for an improved clozapine-like compound has resulted in the selection of a new molecule: JL13 (5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5] benzoxazepine fumarate). Like clozapine, JL13 did not antagonize apomorphine-induced stereotypy and did not produce catalepsy but antagonized apomorphine-induced climbing in rodents (ID50 = 3.9 mg kg-1 s.

Discriminative-stimulus effects of clozapine in squirrel monkeys: comparison with conventional and novel antipsychotic drugs.

The effects of conventional and novel atypical antipsychotic drugs were compared to clozapine in squirrel monkeys that discriminated I.M. injections of clozapine (1.

Glycerol-induced augmentation of sensitivity to endotoxin in rats.

Combined sepsis and rhabdomyolysis result in a mortality rate much higher than that caused by each process alone. An analogous rat model is obtained by simultaneous i.p.

Modulation of the discriminative stimulus effects of cocaine by mu and kappa opioids.

The effects of cocaine alone and after pretreatment with selective mu and kappa opioids were determined in squirrel monkeys trained to discriminate i.m. injections of cocaine from vehicle in a two-lever discrimination procedure.

Gamma globulin prophylaxis to reduce post-transfusion non-A, non-B hepatitis after cardiac surgery with cardiopulmonary bypass.

A prospective, randomized study of immune serum globulin (ISG) for prevention of post-transfusion hepatitis was performed on 196 patients (100 controls without gammaglobulin or placebo and 96 who received ISG) undergoing valve replacement or coronary artery bypass with extracorporeal circulation. The dose of ISG was 2 ml i.m.

[Reciprocal effect of polypeptides and mediators on the ileum of the guinea pig].

The cross influence of polypeptides (substance P, eledoisin) and neurotransmitters (acetylcholine, histamine, 5-hydroxytryptamine, ATP) on isolated guinea pig ileum involved a reduction or loss of muscle sensitivity. After the desensitization induced by one of the neurotransmitters the sensitivity of the ileum longitudinal muscle to polypeptides as estimated by the dissociation constant of the drug-receptor complex, decreased, i.e.

Plasma atropine concentrations determined by radioimmunoassay after single-dose i.v. and i.m. administration.

The plasma concentrations of atropine following i.v. or i.