Differential disruption of response alternation by precipitated Δ9-THC withdrawal and subsequent Δ9-THC abstinence in mice.

In addition to overt somatic symptoms, cannabinoid withdrawal can also manifest as disruptions in motivation and attention. Experimental animal models using operant-conditioning approaches reveal these differences, in either antagonist-precipitated or spontaneous withdrawal models. However, these processes have yet to be characterized in the same subjects simultaneously. To differentiate between motivational and attentional processes disrupted in cannabinoid withdrawal, the current study used a response alternation task in which a fixed-ratio (FR) schedule repeatedly alternated between two spatially distinct response options throughout daily training sessions. This task yielded traditional measures of motivation (e.g., response latency) as well as attention (e.g., responses to the incorrect side). After two weeks of training, male and female C57BL/6 J mice either received vehicle or Δ9-THC (10 mg/kg, s.c.) twice daily for 5 days. On the 6th day, all mice received their final injection of vehicle or Δ9-THC followed 30 min later by injection of the CB1 receptor selective inverse agonist rimonabant (2 mg/kg, i.p.) to precipitate withdrawal. Testing continued for 3 days post-rimonabant to assess how THC abstinence impacted task performance. Whereas rimonabant decreased response rates to equal degrees in THC-treated and vehicle-treated mice, THC-treated mice showed longer session times, longer response latencies, and more errors per reinforcer. Only THC-treated mice showed a longer latency to switch after committing an error reflecting that precipitated withdrawal impacted measures of both motivation and attention. During the 3-day abstinence window, performance of vehicle-treated mice returned to baseline, but THC-treated mice continued to show disruptions in motivational measures. Importantly, attentional measures (errors and latency to switch after an error) were unaffected by THC abstinence. These data suggest that precipitated and "spontaneous" cannabinoid withdrawal may be qualitatively and quantitatively distinct withdrawal conditions with precipitated withdrawal disrupting both attentional and motivational processes, while abstinence may only affect motivation.

Paraquat Inhalation, a Translationally Relevant Route of Exposure: Disposition to the Brain and Male-Specific Olfactory Impairment in Mice.

Epidemiological and experimental studies have associated oral and systemic exposures to the herbicide paraquat (PQ) with Parkinson's disease. Despite recognition that airborne particles and solutes can be directly translocated to the brain via olfactory neurons, the potential for inhaled PQ to cause olfactory impairment has not been investigated. This study sought to determine if prolonged low-dose inhalation exposure to PQ would lead to disposition to the brain and olfactory impairment, a prodromal feature of Parkinson's disease. Adult male and female C57BL/6J mice were exposed to PQ aerosols in a whole-body inhalation chamber for 4 h/day, 5 days/week for 4 weeks. Subsets of mice were sacrificed during and after exposure and PQ concentrations in various brain regions (olfactory bulb, striatum, midbrain, and cerebellum) lung, and kidney were quantified via mass spectrometry. Alterations in olfaction were examined using an olfactory discrimination paradigm. PQ inhalation resulted in an appreciable burden in all examined brain regions, with the highest burden observed in the olfactory bulb, consistent with nasal olfactory uptake. PQ was also detected in the lung and kidney, yet PQ levels in all tissues returned to control values within 4 weeks post exposure. PQ inhalation caused persistent male-specific deficits in olfactory discrimination. No effects were observed in females. These data support the importance of route of exposure in determination of safety estimates for neurotoxic pesticides, such as PQ. Accurate estimation of the relationship between exposure and internal dose is critical for risk assessment and public health protection.

The Internal Clock: A Manifestation of a Misguided Mechanistic View of Causation?

Across various subfields within psychology, mechanistic causation is invoked regularly. When the temporal contiguity of the typical cause-effect relation is violated, mechanistic causation often assigns causal roles to mediating hypothetical constructs to account for observed effects. Two primary consequences of mechanistic causation are that 1) the proposed hypothetical constructs add what many behavior analysts consider an unnecessary step in the causal chain, and 2) these constructs then become the focus of study thereafter diverting attention from more accessible "causes." Constructs do not contribute directly to determining the control of behavior; thus, their reification as "causes" often distracts from variables that do fulfill a causal role. In this review, these consequences are discussed in relation to theories of interval timing proposing an internal clock. Not only has this clock been said to be a cause of behavior in experiments on temporally regulated behavior, but also the clock itself has been a frequent subject of study within the timing literature. Despite descriptive accounts of this sort initially serving a heuristic function for model development, the promotion from descriptive aid to causal factor has the potential to limit much of the heuristic value that mechanistic models of causation can provide to the analysis of behavior. Problems related to construct reification are less likely to be at issue when functional relations and the processes of establishing such behavior are emphasized as alternatives to mechanistic causation alone.

Using heart rate as a physical activity metric.

Physical activity (PA) is critical for a healthy lifestyle. The current study assessed heart rate (HR) as a primary measure of moderate and vigorous PA with four typically developing children. First, individualized HR assessments were conducted to determine moderate and vigorous HR zones. Next, participants engaged in various exercises at a local YMCA facility (i.e., biking, elliptical, basketball, and exergame boxing) to determine how HR during these activities aligned with their individualized HR zones. During exercise bouts, HR was typically above moderate, but below vigorous HR zones for all participants. Additionally, exercises that restricted range of motion (i.e., biking and elliptical) engendered generally lower HR than exercises with greater range of motion. Vocal instructions to exercise at vigorous levels were effective at increasing HR to vigorous levels for one participant. The advantages of using HR as a metric of PA during assessment and intervention are discussed.

Differential reinforcement of low rates differentially decreased timing precision.

Timing processes have been implicated as potential mechanisms that underlie self-controlled choice. To investigate the impact of an intervention that has been shown to increase self-controlled choice on timing processes, accuracy and precision of temporal discrimination were assessed in an 18-s peak procedure (18-s fixed interval trials; 54-s peak trials). During an intervention phase, mice in three treatment groups experienced differential reinforcement of low rate (DRL) schedules of reinforcement of 27 s, 18 s, or 9 s. A fourth group received continued exposure to the peak procedure. After the DRL intervention, timing was reassessed using the peak procedure. In contrast to previous reports, the DRL intervention resulted in less precise timing as indicated by increased peak spread and disrupted single-trial measures of temporal control. These effects were only detected just after the DRL intervention suggesting a transient effect of DRL exposure on timing. The increase in peak spread in the present experiment suggests delay exposure via DRL schedules may produce a "dose-dependent" effect on temporal discrimination, which may also increase self-controlled choice.