Association for Behavior Analysis International

Behavioral pharmacology as a discipline was founded in large part by examining drug effects on basic schedules of reinforcement. Although this remains an important part of the field, the empirical validation of complex behavioral procedures using increasingly sophisticated technology, and the availability of improved agonists and antagonists across drug classes has greatly enlarged the scope of behavioral pharmacology. The purpose of the present symposium is to highlight several recent efforts exploring the effects of drugs on complex behavior. The first speaker will describe the ability of dopamine agonists to induce compulsive-type behavior in rhesus monkeys, and the complex environmental variables maintaining such effects. The second speaker will evaluate potential cognitive-enhancing effects of a5GABAA inverse agonists in rhesus monkeys using delayed matching-to-sample and self-ordered spatial search tasks. The third speaker will discuss drug effects on complex olfactory stimulus control in rats using an olfactory incrementing nonmatch-to-sample procedure in a custom-designed multiscented chamber. The final speaker will discuss the empirical validation of a novel isolated touch-sensitive chamber with squirrel monkeys, and initial studies with cannabinoids.

There is evidence of D2-like dopamine receptor involvement in drug addiction and compulsive behavior. Clinical reports link increases in compulsive behavior (such as pathological gambling) to D3-preferring agonists and, in nonhumans, D2/D3 agonists increase responding for cues previously paired with cocaine or water reinforcement. The current study further explored this finding in rhesus macaques with a history of responding on a PR schedule for food paired with distinct token light stimuli. Four subjects were exposed to an acute drug dosing regimen, and 4 to a chronic regimen of D3-preferring agonist pramipexole administered as a pretreatment. Pramipexole induced high levels of responding when lever presses resulted in token (CS) presentations and no primary reinforcement. When conditioned stimuli were removed from the context, responding was markedly reduced as compared to when tokens were present. Further manipulations have assessed other contextual or behavioral influences by presenting neutral discriminative stimuli, altering the reinforcement schedule, and diminishing the value of the primary reinforcer through both prefeeding and by extending the number of extinction sessions prior to drug pretreatments. Continued research is aimed at assessing whether pramipexole is indeed increasing the value of CSs or perhaps altering typical extinction processes.

It has been suggested that a5GABAA receptor (a5GABAAR) inverse agonists might serve as cognitive enhancers and potential therapeutics for cognitive impairment produced by neurological deterioration. We evaluated the effects of a5GABAAR inverse agonists and comparison drugs on delayed matching-to-sample (DMTS) and self-ordered spatial search (SOSS) performances in rhesus monkeys. In the DMTS procedure, accuracy decreased as the delay between sample and choice stimuli increased. In the SOSS procedure, accuracy decreased as the number of stimuli requiring sequential nonrepeat touches increased. The nonselective benzodiazepine agonist triazolam, the cholinergic antagonist scopolamine, and the a1-preferential GABAAR agonist zolpidem reduced DMTS and SOSS accuracy. Triazolam and scopolamine, but not zolpidem, decreased trials completed. The low and medium efficacy inverse agonists PWZ-029 and RY-23 were without effect, whereas the high efficacy inverse agonist RY-24 decreased trials completed without affecting accuracy. The putative cognitive enhancers methylphenidate, a dopamine uptake inhibitor, and nicotine, a cholinergic agonist, did not improve accuracy in either procedure. Methylphenidate, but not nicotine, reduced trials completed. Future research should determine the pharmacokinetic profile of a5GABAAR inverse agonists in monkeys and also their effects in animals with neurological deterioration to clarify the therapeutic potential of a5GABAAR inverse agonists.

Complex forms of stimulus control in rodents are readily studied using olfactory stimuli. These permit the development of preparations useful for the analysis of drug effects on complex behavior. The olfactory incrementing non-match-to-sample (INMTS) procedure is designed to provide a within-session analysis of stimulus control by an increasing number of sample stimuli and is thought by some to be analogous to the digit span task in humans. Our lab is exploring this procedure as a baseline for behavioral pharmacology in rats. In the initial trial of each session, 1 stimulus cup marked with a distinct olfactory stimulus was present and responding to it was reinforced. Each subsequent trial added a new olfactory stimulus and responding to the new stimulus was always reinforced (nonmatching). A performance task was included to control for any nonmnemonic drug effects. I will present data from a series of studies of several different drugs, but only the noncompetitive NMDAr antagonist, dizocilpine (MK 801) has produced selective impairment on the INMTS task.

Despite the increasing sophistication and affordability of touch-sensitive technology, its use in the behavioral and pharmacological sciences has been limited. The present talk will describe the design and empirical validation of a novel isolated touch-sensitive operant conditioning chamber for use with squirrel monkeys. In addition, an overview of studies assessing the effects of cannabinoids on repeated acquisition and discrimination reversal will be presented, and the virtues and limits of this approach to evaluating drugs will be discussed. Results from ongoing studies show that response rates approximate those obtained using conventional manipulanda (lever or key) and provide evidence of the reliability and sensitivity of the screen as a response transducer. Results also indicate the touchscreen can be used to seamlessly transition across experimental protocols within the same session. Data from studies with cannabinoid agonists reveal dose-related effects on performance that agree with previous reports using conventional approaches, assuring the reliability of this approach. The ability to program (1) near-limitless variety of complex stimuli, and (2) variability in spatial location define 2 major advantages of the touch-sensitive operant apparatus.