Maria G. Valdovinos

Effects of risperidone on destructive behavior of persons with developmental disabilities: III. Functional analysis.

Functional analyses were conducted during a double-blind, placebo-controlled study of the atypical antipsychotic medication risperidone with 13 individuals. Risperidone was effective in reducing destructive behavior (compared to placebo) for 10 participants. For 7 of these responders, an undifferentiated pattern of responding occurred across their baseline functional analysis conditions (i.e., a similar rate of responding across conditions), and risperidone treatment produced nonspecific reductions of their destructive behavior across functional analysis conditions. For the remaining 3 responders, a differentiated pattern of responding occurred across their baseline functional analysis conditions (i.e., an elevated rate of responding occurred in a specific condition), and risperidone treatment produced function-specific reductions of their destructive behavior.

Medical and Behavioral Symptoms as Potential Medication Side Effects in Adults with Developmental Disabilities.

The incidence of medical and behavioral symptoms that could occur as side effects of psychotropic medication was assessed in a sample of 30 adults with developmental disabilities. Using a retrospective chart review method, we measured symptoms in six a priori classes of potential side effects over a 2-year period. The majority of side effects involved apparent effects of the psychotropic medications on behavior, mood, or sleep. Different patterns of changes in medication prescription, in relation to recorded side effects, were observed. Overall, there was a significant positive relation between the number of potential side effects recorded and the number of psychotropic medication changes made. Our findings suggest several patterns of side effects associated with psychotropic medication use.

Nociceptor and age specific effects of REM sleep deprivation induced hyperalgesia

REM sleep deprivation (REMSD) has been shown to increase rates of negatively reinforced operant behavior, but not operant responding maintained by positive reinforcement. The reason for this differential effect is currently unknown. We hypothesize that REMSD can increase sensitivity to noxious stimuli. In the present study, we sought to determine if REMSD was associated with a change in response to noxious heat (i.e., altered nociceptive sensitivity). Two groups of rats, aged 6 and 22 months, were subjected to hotplate algesia testing at two different temperatures (44 and 52 degrees C). Initially, baseline numbers of responses and total response time were obtained at 44 degrees C. Animals then were exposed to 48 h of REMSD or control conditions. The frequency and duration of hindpaw responses (licking and guarding) increased for young animals only after REMSD and none of the control conditions. Old rats showed increased duration of nocifensive responding after REMSD and tank control conditions without a change in the number of responses at 44 degrees C. Latency to first nocifensive response was significantly longer in the 44 degrees C hotplate tests, but decreased to levels observed throughout the 52 degrees C hotplate tests following REMSD and TC conditions. These findings suggest that REMSD increases nociceptive sensitivity under conditions of sustained, selective C nociceptor activation (42 degrees C), but not under conditions of phasic A-delta activation (52 degrees C). The findings also indicate that age can be a significant variable in REMSD studies.

Multimodal evaluation of risperidone for destructive behavior: functional analysis, direct observations, rating scales, and psychiatric impressions.

Risperidone, an atypical neuroleptic, has become a popular option for treating destructive behaviors of persons with developmental disabilities. A few studies have been conducted that evaluate the effects of risperidone on destructive behavior; however, none of these studies have combined objective measures with rating scales to evaluate the effects of risperidone on destructive behavior across home and clinical settings. This study evaluated the wide range of effects of risperidone on destructive behavior of 2 persons with developmental disabilities using weekly functional analysis sessions, daily observations, hourly home data, weekly rating scales, and monthly psychiatric impressions. Results indicate that risperidone does decrease destructive behavior and that, for the most part, all of the various measures yielded similar results.

Prevalence and Correlates of Psychotropic Medication Use among Adults with Developmental Disabilities: 1970–2000

Publisher Summary This chapter discusses the prevalence and correlates of psychotropic medication use, among adults with developmental disabilities. People with mental retardation are among the most medicated in our society. Throughout the years, studies have measured the prevalence of psychotropic medication use, among people with developmental disabilities, and have attempted to identify the factors that are related to the prevalent use of psychotropic medication in this population. Anxiolytics or sedatives include medications, such as barbiturate-like medications, Benzodiazepines, anti-histamines, and Buspirone. These medications are generally prescribed as anti-anxiety medication that can also be used to aid in sleep problems, control epilepsy, and stabilize mood. Data obtained from prevalence studies might provide insight into the current status of psychotropic medication use, but these figures inform the public only about what is occurring exclusively in that geographic area or setting at that particular time. It is suggested that empirical research should be conducted to determine the appropriate use of psychotropic medication.

A behavior-analytic conceptualization of the side effects of psychotropic medication

A range of behavior—much deemed problematic by society—is treated with behavioral methods or psychotropic medications. Although the processes associated with behavioral interventions have been investigated using conceptual, experimental, and applied analyses, less is known about the behavioral processes associated with the use of psychotropic medication. Psychotropic drugs produce at least two types of effects of behavioral interest: (a) primary effects of drug action on target behaviors and (b) side effects that change the target or other behavior. Although an empirical literature exists regarding the former effects, little attention has been given to the latter topic. In this paper we offer a conceptual analysis of the side effects of psychotropic medication. We propose that the side effects of various drugs can influence behavior by functioning as motivating operations, conditional or discriminative stimuli, or by establishing new response-reinforcer relations. This conceptualization may facilitate the empirical analysis of how psychotropic drugs change behavior.

Serotonin2A/C receptors mediate the aggressive phenotype of TLX gene knockout mice

Deleting the tailless (TLX) gene in mice produces a highly aggressive phenotype yet to be characterized in terms of heterozygous animals or neurotransmitter mechanisms. We sought to establish pharmacological control over aggression and study the role of serotonin (5-HT)(2A/C) receptors in mediating changes in aggression. We analyzed aggression in mice heterozygous (+/-) or homozygous (-/-) for the TLX gene and wild-types (+/+) using a resident-intruder paradigm. No +/+ mice were aggressive, 36% of +/- TLX and 100% of -/- TLX mice showed aggression. Dose-effect functions were established for clozapine (0.1-1.5mg/kg, ip), ketanserin (0.3-1.25 mg/kg, ip), and (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(±)DOI] (0.5-2.0 mg/kg, ip). Injecting clozapine decreased the frequency and duration of attacks for +/- TLX and -/- TLX mice. Clozapine did not decrease grooming in either +/- TLX or -/- TLX mice but may have increased locomotion for -/- TLX mice. Injecting ketanserin, a 5-HT(2A/C) receptor antagonist, produced differential decreases in frequency and latency to aggression between genotypes and corresponding increases in locomotor behavior. Injecting (±)DOI, a 5-HT(2A/C) receptor agonist, increased the frequency and duration of attacks, decreased the latency to attacks, and decreased locomotion in +/- and -/- TLX mice. Results of the current study suggest aggression displayed by TLX null and heterozygous mice involves 5-HT(2A/C) receptors.

Parametric analysis of thermal preference following sleep deprivation in the rat

A thermal preference task was used to assess the effects of sleep deprivation on nociceptive behavior using hot and cool stimuli. The thermal preference apparatus allowed male rats to move freely from a hot thermal plate (44.7°C) to an adjacent plate at neutral (33.5°C) or cold temperatures (1.3-11°C). Investigators recorded occupancy on the colder side, frequency of movements between the 2 compartments, and first escape latency from the cold side. Parametric analysis of thermal preference indicated that behavioral allocation was related to temperature ranges previously associated with activation of thermal nociceptors. A 50% occupancy rate was determined from a stimulus-response function identifying 1.3°C vs. 44.7°C as optimal temperatures. This temperature combination was then used to test the effects of sleep deprivation for 48h using the pedestal-over-water method on response allocation to the 2 temperature zones. Sleep deprivation decreased time spent on the cooled plate. Cumulative occupancy indicated differential effects for sleep deprivation with the rats preferring to remain on the hot side vs. the cold side, suggesting that sleep deprivation increased the nociceptive properties of the cold stimulus.

Possible role for the 5-HT1A receptor in the behavioral effects of REM sleep deprivation on free-operant avoidance responding in rat

RationaleREM sleep deprivation (REMSD) has been shown to increase rates of free-operant avoidance responding. Depletion of 5-hydroxytryptamine (5-HT, serotonin) levels produces similar effects on responding.ObjectiveWe studied whether the pharmacological activation of the 5-HT1A receptor would produce effects on avoidance responding similar to REMSD and depleted 5-HT levels.MethodsRats were trained to lever press on a free-operant avoidance task. Dose-effect functions were established for 8-OH-DPAT (a 5-HT1A receptor agonist) (0.1–1.0xa0mg/kg) and WAY 100635 (a 5-HT1A receptor antagonist) (0.1–1.0xa0mg/kg). Rats were then exposed to REMSD (48xa0h) or equivalent control conditions, and then administered 8-OH-DPAT (0.6xa0mg/kg) and/or WAY 100635 (0.025–0.1xa0mg/kg).ResultsInjections of 8-OH-DPAT increased rates of avoidance responding in a dose-dependent manner, while WAY 100635 did not alter responding. The effect of 8-OH-DPAT was antagonized by pre-injection of WAY 100635. REMSD and injections of 8-OH-DPAT increased rates of avoidance responding and the effects of both manipulations were reversed by pre-injection of WAY 100635.ConclusionsActivation of the 5-HT1A receptor may be a mechanism by which REMSD increases rates of free-operant avoidance responding.

Varied effects of conventional antiepileptics on responding maintained by negative versus positive reinforcement.

We analyzed the effects of four conventional antiepileptic drugs (AEDs) - carbamazepine (CBZ), ethosuximide (ETH), phenytoin (PHT), and valproate (VPA) - on operant behavior maintained by negative or positive reinforcement contingencies. Rats were trained to lever press on a free-operant avoidance schedule or variable-interval (VI) schedule of appetitive reinforcement. Dose-effect functions were separately established on each reinforcement contingency for CBZ (12.5-100 mg/kg), ETH (25-200 mg/kg), PHT (12.5-50 mg/kg), and VPA (50-400 mg/kg). CBZ and PHT reduced responding on free-operant avoidance and VI appetitive reinforcement tasks, with positively reinforced behavior reduced at lower drug dosages than negatively reinforced responding. ETH and VPA reduced responding on the VI appetitive reinforcement task, but did not alter behavior maintained on the free-operant avoidance schedule. Our results suggest that conventional AEDs vary in their effect on operant behavior, depending on the type of reinforcement process maintaining responding.