Sex Differences In Extinction Research Articles

Sex differences in extinction and reinstatement of nicotine discrimination in rats: The effects of reinforcer devaluation.

Sex differences in extinction and reinstatement of nicotine discrimination in rats: The effects of reinforcer devaluation.

Sex differences in extinction to negative stimuli: Event-related brain potentials.

There are controversial observations regarding whether females have a longer time to extinction than men, which may be related to different levels of conditioning acquisition and/or the influence of the menstrual cycle. We explored the electrophysiological evidence of sex differences in extinction.In this study, females in the luteal phase and menstrual phase were examined for event-related potential (ERP) and evidence of attention allocation in the conditioning model using electroencephalogram recordings. A group of male participants was also included and compared.Women in the luteal phase had a higher difference waveform of P3 amplitude to conditioned stimulus (CS) in the extinction phase than women in the menstrual phase and men. There was a shorter latency of P3 to CS+ in men than in women in the extinction phase, suggesting that men react faster than women to unconditioned stimulus (US) expectation. Our study revealed that women in the luteal phase allocated more attentive resources to the expectation of a US. In contrast, men displayed faster expectation of the extinguished US than women. Our results support the superiority of ERP technology in documenting the neural mechanism of the extinction process.

Brain-derived neurotrophic factor and addiction: Pathological versus therapeutic effects on drug seeking

Many abused drugs lead to changes in endogenous brain-derived neurotrophic factor (BDNF) expression in neural circuits responsible for addictive behaviors. BDNF is a known molecular mediator of memory consolidation processes, evident at both behavioral and neurophysiological levels. Specific neural circuits are responsible for storing and executing drug-procuring motor programs, whereas other neural circuits are responsible for the active suppression of these “seeking” systems. These seeking-circuits are established as associations are formed between drug-associated cues and the conditioned responses they elicit. Such conditioned responses (e.g. drug seeking) can be diminished either through a passive weakening of seeking- circuits or an active suppression of those circuits through extinction. Extinction learning occurs when the association between cues and drug are violated, for example, by cue exposure without the drug present. Cue exposure therapy has been proposed as a therapeutic avenue for the treatment of addictions. Here we explore the role of BDNF in extinction circuits, compared to seeking-circuits that “incubate” over prolonged withdrawal periods. We begin by discussing the role of BDNF in extinction memory for fear and cocaine-seeking behaviors, where extinction circuits overlap in infralimbic prefrontal cortex (PFC). We highlight the ability of estrogen to promote BDNF-like effects in hippocampal–prefrontal circuits and consider the role of sex differences in extinction and incubation of drug-seeking behaviors. Finally, we examine how opiates and alcohol “break the mold” in terms of BDNF function in extinction circuits.This article is part of a Special Issue entitled SI:Addiction circuits.

Sex differences in extinction recall in posttraumatic stress disorder: A pilot fMRI study

Recent research has found that individuals with posttraumatic stress disorder (PTSD) exhibit an impaired memory of fear extinction compounded by deficient functional activation of key nodes of the fear network including the amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (dACC). Research has shown these regions are sexually dimorphic and activate differentially in healthy men and women during fear learning tasks. To explore biological markers of sex differences following exposure to psychological trauma, we used a fear learning and extinction paradigm together with functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) to assess 31 individuals with PTSD (18 women; 13 men) and 25 matched trauma-exposed healthy control subjects (13 women; 12 men). Whereas no sex differences appeared within the trauma-exposed healthy control group, both psychophysiological and neural activation patterns within the PTSD group indicated deficient recall of extinction memory among men and not among women. Men with PTSD exhibited increased activation in the left rostral dACC during extinction recall compared with women with PTSD. These findings highlight the importance of tracking sex differences in fear extinction when characterizing the underlying neurobiological mechanisms of PTSD psychopathology.

Neonatal Isolation Stress Potentiates Cocaine Seeking Behavior in Adult Male and Female Rats

Little is known with regard to how sex and stress might interact as vulnerability factors in cocaine abuse. In this study, we compared the effects of neonatal isolation stress on cocaine self-administration under extended access conditions and on subsequent responding in a cue-induced reinstatement paradigm in adult male and female rats. Pups from each litter were subjected to either neonatal isolation (1 h/day) or brief daily handling from postnatal day 2 through 12. Adults rats were then trained to self-administer cocaine, and once they acquired lever responding for cocaine under a fixed ratio 1 schedule, they were given 24-h access to intravenous cocaine infusions (1.5 mg/kg) that were available in discrete trials (4, 10 min trials/h) for 7 consecutive days. At 10 days after the last discrete trial session, responding was assessed during six to eight 1-h extinction sessions that were followed by a 1-h cue-induced reinstatement session. Results revealed that females took more cocaine than did males over the 7-day discrete trial self-administration period and tended to respond at higher levels during the initial extinction sessions. Although intake did not differ between handled control rats and isolated rats under extended access conditions, stress effects were observed under subsequent extinction and cue-induced reinstatement testing conditions with isolated rats responding at higher levels during both phases. Notably, stress seemed to obscure sex differences in extinction responding such both isolated males and females responded at high levels. These findings demonstrate robust and enduring effects of neonatal isolation stress on cocaine seeking behavior in adult male and female rats.

Morphine-induced conditioned taste aversions: assessment of sexual dimorphism

Although sex differences in taste aversions have been reported with emetics such as lithium chloride (LiCl), little is known whether such findings generalize to other aversion-inducing drugs, including recreational compounds. One particular class of recreational compounds that induces taste aversions but that has not been examined for sex differences in its aversive properties is the opioids. To assess sex differences in the aversive properties of the opioids, Experiment 1 examined the acquisition and extinction of morphine-induced taste aversions in male and female rats. To determine whether the specific parametric conditions used in Experiment 1 would support sex differences in general, Experiment 2 examined possible sex differences in the acquisition and extinction of LiCl-induced taste aversions, a compound for which sex differences have been previously reported. During acquisition, male and female rats were given 20-min access to a novel saccharin solution and injected with either morphine (0, 10, 18 and 32 mg/kg sc; Experiment 1) or LiCl (0, 0.3, 0.6 and 1.2 mEq sc; Experiment 2) every fourth day for a total of four conditioning trials. During extinction, subjects were allowed access to saccharin but were not injected (for a total of eight trials). There were no sex differences in acquisition with either morphine or LiCl. There were also no sex differences in extinction with morphine; however, sex differences were found with LiCl, an effect consistent with prior assessments with this drug. The basis for and implications of the differences in the effects of sex on morphine- and LiCl-induced taste aversions were discussed.

Effects of early postnatal gonadal steroids on extinction of a continuously food-rewarded running response

In the present work the existence of sex differences (Experiment 1) on the acquisition and extinction of a continuously reinforced response in a short and narrow runway (100 × 9 × 10 cm) were investigated. In addition to the investigation of the basic sex differences in Experiment 1, the effect of postpuberal gonadectomy of male and female rats and the role of the early postnatal gonadal steroids on these situations were also examined in Experiments 2 and 3, respectively. In all experiments, no sex differences were found in acquisition. However, males extinguished faster than female rats. Gonadectomy of both sexes in adulthood, although it increases their latencies in acquisition, did not affect the differences between sexes during extinction. In contrast, in Experiment 3 female androgenization and male orchidectomy on day one after birth reversed the direction of sex differences found between control rats in the extinction period. Our findings suggests that the observed sex differences in extinction may be due to an underlying sexual dimorphism in the response inhibition process.

Sex differences in extinction of food-rewarded approach responses

Female rats exhibited slower extinction of a food-rewarded running response than did males, but here was no sex difference in extinction of a barpress response that was rewarded by food. It is suggested that sex differences in exploratory activity underlie the differences in extinction.