Contextual extinction of drug-associated discriminative stimuli fails to attenuate drug-vs-food choice in rhesus monkeys.

Relapse within the context of a substance use disorder can be triggered by cues that function as discriminative stimuli to signal contingencies of drug availability and promote drug-taking behavior. Extinction procedures can weaken this association between drug-associated cues and drug-taking behavior and may reduce the probability of relapse. This study evaluated a regimen of extinction training on cocaine and heroin self-administration in rhesus monkeys under a drug-vs-food choice procedure.

Cocaine-associated decision-making: Toward isolating preference.

Ever-increasing evidence suggests that substance use disorder is mediated by decision-making processes, and as such, providing nondrug alternatives can shift maladaptive preferences away from drug reinforcers, such as cocaine. Of note, a recent hypothesis suggests that preference for cocaine is simply a byproduct of cocaine intake, such that the 'direct' effects of cocaine weaken the impact of non-drug alternatives while measuring choice. Conversely, existing quantitative theories of decision-making suggest preference is determined by various dimensions of concurrent reinforcers that in turn determine the relative value of available alternatives.

Remifentanil maintains lower initial delayed nonmatching-to-sample accuracy compared to food pellets in male rhesus monkeys.

Emerging human laboratory and preclinical drug self-administration data suggest that a history of contingent abused drug exposure impairs performance in operant discrimination procedures, such as delayed nonmatching-to-sample (DNMTS), that are hypothesized to assess components of executive function. However, these preclinical discrimination studies have exclusively used food as the reinforcer and the effects of drugs as reinforcers in these operant procedures are unknown. The present study determined effects of contingent intravenous remifentanil injections on DNMTS performance hypothesized to assess 1 aspect of executive function, working memory.

Effects of 21-day d-amphetamine and risperidone treatment on cocaine vs food choice and extended-access cocaine intake in male rhesus monkeys.

Background: Clinical trial data suggest amphetamine treatment is most efficacious in moderate to high frequency cocaine users. However, preclinical studies have examined amphetamine treatment effects under relatively limited cocaine access conditions with low to moderate cocaine intakes. This study determined d-amphetamine treatment effects on cocaine self-administration in rhesus monkeys under cocaine access conditions allowing for high daily cocaine intake.

Chronic cocaine exposure in adolescence: Effects on spatial discrimination reversal, delay discounting, and performance on fixed-ratio schedules in mice.

Adolescence is marked by the continued development of the neural pathways that support choice and decision-making, particularly those involving dopamine signaling. Cocaine exposure during adolescence may interfere with this development and manifest as increased perseveration and delay discounting in adulthood, behavioral processes that are related to drug addiction. Adolescent mice were exposed to 30mg/kg/day of cocaine (n=11) or saline vehicle (n=10) for 14days and behavior was assessed in adulthood.

Abuse-related neurochemical and behavioral effects of cathinone and 4-methylcathinone stereoisomers in rats.

Cathinone and many of its analogs produce behavioral effects by promoting transporter-mediated release of the monoamine neurotransmitters dopamine, norepinephrine and/or serotonin. Stereoselectivity is one determinant of neurochemical and behavioral effects of cathinone analogs. This study compared effectiveness of the S(-) and R(+) enantiomers of cathinone and 4-methylcathinone to produce in vitro monoamine release and in vivo abuse-related behavioral effects in rats.

Spatial discrimination reversal and incremental repeated acquisition in adolescent and adult BALB/c mice.

Adolescence is characterized by neural and behavior development that includes increases in novel experiences and impulsive choice. Experimental rodent models can characterize behavior phenotypes that typify adolescence. The present experiment was designed to characterize differences between adolescent (post-natal day (PND) 34-60) and adult (PND 70-96) BALB/c mice using a response-initiated spatial discrimination reversal (SDR) and incremental repeated acquisition of response chains (IRA) procedures.

Use of Preclinical Drug vs. Food Choice Procedures to Evaluate Candidate Medications for Cocaine Addiction.

Drug addiction is a disease that manifests as an inappropriate allocation of behavior towards the procurement and use of the abused substance and away from other behaviors that produce more adaptive reinforcers (e.g. exercise, work, family and social relationships).

Effects of environmental and pharmacological manipulations on a novel delayed nonmatching-to-sample 'working memory' procedure in unrestrained rhesus monkeys.

Background: Working memory is a domain of 'executive function.' Delayed nonmatching-to-sample (DNMTS) procedures are commonly used to examine working memory in both human laboratory and preclinical studies.

New Method: The aim was to develop an automated DNMTS procedure maintained by food pellets in rhesus monkeys using a touch-sensitive screen attached to the housing chamber.

Delay-specific stimuli and genotype interact to determine temporal discounting in a rapid-acquisition procedure.

The importance of delay discounting to many socially important behavior problems has stimulated investigations of biological and environmental mechanisms responsible for variations in the form of the discount function. The extant experimental research, however, has yielded disparate results, raising important questions regarding Gene X Environment interactions. The present study determined the influence of stimuli that uniquely signal delays to reinforcement on delay discounting in two inbred mouse strains using a rapid-acquisition procedure.

Preclinical Assessment of Lisdexamfetamine as an Agonist Medication Candidate for Cocaine Addiction: Effects in Rhesus Monkeys Trained to Discriminate Cocaine or to Self-Administer Cocaine in a Cocaine Versus Food Choice Procedure.

Background: Chronic amphetamine treatment decreases cocaine consumption in preclinical and human laboratory studies and in clinical trials. Lisdexamfetamine is an amphetamine prodrug in which L-lysine is conjugated to the terminal nitrogen of d-amphetamine. Prodrugs may be advantageous relative to their active metabolites due to slower onsets and longer durations of action; however, lisdexamfetamine treatment's efficacy in decreasing cocaine consumption is unknown.

Effects of the kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) on cocaine versus food choice and extended-access cocaine intake in rhesus monkeys.

The dynorphin/kappa opioid receptor (KOR) system has been implicated as one potential neurobiological modulator of the abuse-related effects of cocaine and as a potential target for medications development. This study determined effects of the KOR antagonist nor-binaltorphimine (nor-BNI) on cocaine self-administration under a novel procedure that featured two daily components: (1) a 2-hour 'choice' component (9:00-11:00 am) when monkeys could choose between food pellets and cocaine injections (0-0.1 mg/kg per injection, intravenous) and (2) a 20-hour 'extended-access' component (noon to 8:00 am) when cocaine (0.

A generalized matching law analysis of cocaine vs. food choice in rhesus monkeys: effects of candidate 'agonist-based' medications on sensitivity to reinforcement.

Background: We have previously demonstrated reductions in cocaine choice produced by either continuous 14-day phendimetrazine and d-amphetamine treatment or removing cocaine availability under a cocaine vs. food choice procedure in rhesus monkeys. The aim of the present investigation was to apply the concatenated generalized matching law (GML) to cocaine vs.

Attention and psychophysics in the development of stimulus control.

Rats responded in a six-stimulus, two-response temporal classification procedure. A successive-reversal design was used in which the relationship between stimulus class (short vs. long) and correct comparison location (left or right) reversed every 15 sessions.

Dietary nimodipine delays the onset of methylmercury neurotoxicity in mice.

Adult-onset methylmercury (MeHg) exposure is thought to result primarily in sensory and motor deficits but effects on learning are poorly understood. One mechanism by which chronic MeHg may exert its neurotoxicity is via sustained disruption of intracellular calcium homeostasis, with a consequent increase of intracellular Ca(2+) ions in vulnerable neurons. A biochemically heterogeneous group of compounds, calcium channel blockers, have been shown in vitro to attenuate MeHg's toxicity.

A quantitative analysis of the effects of qualitatively different reinforcers on fixed ratio responding in inbred strains of mice.

Previous studies of inbred mouse strains have shown reinforcer-strain interactions that may potentially mask differences among strains in memory performance. The present research examined the effects of two qualitatively different reinforcers (heterogeneous mix of flavored pellets and sweetened-condensed milk) on responding maintained by fixed-ratio schedules of reinforcement in three inbred strains of mice (BALB/c, C57BL/6, and DBA/2). Responses rates for all strains were a bitonic (inverted U) function of the size of the fixed-ratio schedule and were generally higher when responding was maintained by milk.

The dig task: a simple scent discrimination reveals deficits following frontal brain damage.

Cognitive impairment is the most frequent cause of disability in humans following brain damage, yet the behavioral tasks used to assess cognition in rodent models of brain injury is lacking. Borrowing from the operant literature our laboratory utilized a basic scent discrimination paradigm in order to assess deficits in frontally-injured rats. Previously we have briefly described the Dig task and demonstrated that rats with frontal brain damage show severe deficits across multiple tests within the task.

A discrimination task used as a novel method of testing decision-making behavior following traumatic brain injury.

Traumatic brain injury (TBI) results in a multitude of deficits following injury. Some of the most pervasive in humans are the changes that affect frontally-mediated cognitive functioning, such as decision making. The assessment of decision-making behavior in rodents has been extensively tested in the field of the experimental analysis of behavior.

Rapid acquisition of bias in signal detection: dynamics of effective reinforcement allocation.

We investigated changes in bias (preference for one response alternative) in signal detection when relative reinforcer frequency for correct responses varied across sessions. In Experiment 1, 4 rats responded in a two-stimulus, two-response identification procedure employing temporal stimuli (short vs. long houselight presentations).