SignificanceDecades of research have fostered the now-prevalent assumption that noncrop habitat facilitates better pest suppression by providing shelter and food resources to the predators and parasitoids of crop pests. Based on our analysis of the largest pest-control database of its kind, noncrop habitat surrounding farm fields does affect multiple dimensions of pest control, but the actual responses of pests and enemies are highly variable across geographies and cropping systems. Because noncrop habitat often does not enhance biological control, more information about local farming contexts is needed before habitat conservation can be recommended as a viable pest-suppression strategy. Consequently, when pest control does not benefit from noncrop vegetation, farms will need to be carefully comanaged for competing conservation and production objectives.
Managing agricultural landscapes to support biodiversity and ecosystem services is a key aim of a sustainable agriculture. However, how the spatial arrangement of crop fields and other habitats in landscapes impacts arthropods and their functions is poorly known. Synthesising data from 49 studies (1515 landscapes) across Europe, we examined effects of landscape composition (% habitats) and configuration (edge density) on arthropods in fields and their margins, pest control, pollination and yields. Configuration effects interacted with the proportions of crop and non-crop habitats, and species' dietary, dispersal and overwintering traits led to contrasting responses to landscape variables. Overall, however, in landscapes with high edge density, 70% of pollinator and 44% of natural enemy species reached highest abundances and pollination and pest control improved 1.7-and 1.4-fold respectively. Arable-dominated landscapes with high edge densities achieved high yields. This suggests that enhancing edge density in European agroecosystems can promote functional biodiversity and yield-enhancing ecosystem services.
Relapse vulnerability in cocaine dependence is rooted in genetic and environmental determinants, and propelled by both impulsivity and the responsivity to cocaine-linked cues ('cue reactivity'). The serotonin (5-hydroxytryptamine, 5-HT) 5-HT 2C receptor (5-HT 2C R) within the medial prefrontal cortex (mPFC) is uniquely poised to serve as a strategic nexus to mechanistically control these behaviors. The 5-HT 2C R functional capacity is regulated by a number of factors including availability of active membrane receptor pools, the composition of the 5-HT 2C R macromolecular protein complex, and editing of the 5-HT 2C R pre-mRNA. The one-choice serial reaction time (1-CSRT) task was used to identify impulsive action phenotypes in an outbred rat population before cocaine self-administration and assessment of cue reactivity in the form of lever presses reinforced by the cocaine-associated discrete cue complex during forced abstinence. The 1-CSRT task reliably and reproducibly identified high impulsive (HI) and low impulsive (LI) action phenotypes; HI action predicted high cue reactivity. Lower cortical 5-HT 2C R membrane protein levels concomitant with higher levels of 5-HT 2C R:postsynaptic density 95 complex distinguished HI rats from LI rats. The frequency of edited 5-HT 2C R mRNA variants was elevated with the prediction that the protein population in HI rats favors those isoforms linked to reduced signaling capacity. Genetic loss of the mPFC 5-HT 2C R induced aggregate impulsive action/cue reactivity, suggesting that depressed cortical 5-HT 2C R tone confers vulnerability to these interlocked behaviors. Thus, impulsive action and cue reactivity appear to neuromechanistically overlap in rodents, with the 5-HT 2C R functional status acting as a neural rheostat to regulate, in part, the intersection between these vulnerability behaviors.
Serotonin (5-HT) controls affective and motivational aspects of palatable food and drug reward and the 5-HT2C receptor (5-HT2CR) has emerged as a key regulator in this regard. We have evaluated the efficacy of a selective 5-HT2CR agonist, WAY 163909, in cocaine and sucrose self-administration and reinstatement assays employing parallel experimental designs in free-fed rats. WAY 163909 dose-dependently reduced the reinforcing efficacy of cocaine (ID50=1.19 mg/kg) and sucrose (ID50=0.7 mg/kg) as well as reinstatement (ID50=0.5 mg/kg) elicited by exposure to cocaine-associated contextual cues, but not sucrose-associated contextual cues. The ID50 of WAY 163909 predicted to decrease the reinforcing efficacy of cocaine or sucrose as well as reinstatement upon exposure to cocaine-associated cues was ~5–12-fold lower than that predicted to suppress horizontal ambulation (ID50 = 5.89 mg/kg) and ~2-5-fold lower than that predicted to suppress vertical activity (ID50= 2.3 mg/kg). Thus, selective stimulation of the 5-HT2CR decreases the reinforcing efficacy of cocaine and sucrose in freely-fed rats, but differentially alters the incentive-salience value of cocaine- vs. sucrose-associated cues at doses that do not impair locomotor activity. Future research is needed to tease apart the precise contribution of 5-HT2CR neurocircuitry in reward and motivation and the learning and memory processes that carry the encoding for associations between environmental cues and consumption of rewarding stimuli. A more complete preclinical evaluation of these questions will ultimately allow educated proof-of-concept trials to test the efficacy of selective 5-HT2CR agonists as adjunctive therapy in chronic health maladies including obesity, eating disorders and drug addiction.
Relapse to cocaine dependence, even after extended abstinence, involves a number of liability factors including impulsivity (predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences) and cue reactivity (sensitivity to cues associated with cocaine-taking which can promote cocaine-seeking). These factors have been mechanistically linked to serotonin (5-hydroxytryptamine, 5-HT) signaling through the 5-HT 2A receptor (5-HT 2A R) and 5-HT 2C R; either a selective 5-HT 2A R antagonist or a 5-HT 2C R agonist suppresses impulsivity and cocaine-seeking in preclinical models. We conducted proof-of-concept analyses to evaluate whether a combination of 5-HT 2A R antagonist plus 5-HT 2C R agonist would have synergistic effects over these liability factors for relapse as measured in a 1-choice serial reaction time task and cocaine self-administration/reinstatement assay. Combined administration of a dose of the selective 5-HT 2A R antagonist M100907 plus the 5-HT 2C R agonist WAY163909, each ineffective alone, synergistically suppressed cocaine-induced hyperactivity, inherent and cocaine-evoked impulsive action, as well as cue-and cocaine-primed reinstatement of cocaine-seeking behavior. The identification of synergism between a 5-HT 2A R antagonist plus a 5-HT 2C R agonist to attenuate these factors important in relapse indicates the promise of a bifunctional ligand as an anti-addiction pharmacotherapeutic, setting the stage to develop new ligands with improved efficacy, potency, selectivity, and in vivo profiles over the individual molecules. KEYWORDS: 1-Choice serial reaction time task, 5-HT 2A receptor, 5-HT 2C receptor, cocaine, cue reactivity, impulsivity, self-administration, serotonin D ependence on the psychostimulant cocaine is marked by problematic vulnerability to relapse even years into abstinence. 1,2 Two important liability factors that contribute to relapse are impulsivity (predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences) 3 and cue reactivity (sensitivity to cues associated with cocaine-taking that can promote cocaine-seeking). 4,5 Impulsivity and cue reactivity appear to be interrelated in human cocaine users, 6 and new pharmacotherapeutic strategies that effectively diminish both are likely to enhance abstinence in the highly vulnerable population of cocaine-dependent individuals.The underlying neurobiology of these liability factors includes a regulatory role for serotonin (5-HT; 5-hydroxytryptamine) neurotransmission. The actions of 5-HT in neurons are transduced by at least 14 subtypes of 5-HT receptors (5-HT X Rs) which are presently grouped into seven families (5-HT 1 R−5-HT 7 R) according to their structural and functional characteristics. 7−9 Selective blockade of the 5-HT 2A R 10−12 or activation of the 5-HT 2C R 10,13,14 consistently reduces impulsivity as measured by premature responses assessed in the 1-or 5-choice serial reaction time (1-or 5-CSRT) task, a preclinical Special Issue: Celebratin...
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