Enhancement of auditory fear conditioning after housing in a complex environment is attenuated by prior treatment with amphetamine

Abstract

Prior exposure to drugs of abuse has been shown to occlude the structural plasticity associated with living in a complex environment. Amphetamine treatment may also occlude some cognitive advantages normally associated with living in a complex environment. To test this hypothesis we examined the influence of prior exposure to amphetamine on fear conditioning in rats housed in either a standard or complex environment. Housing in a complex environment facilitated fear learning to an auditory conditioned stimulus (CS), but not to the training context, relative to animals housed singly or in a social group. Prior treatment with amphetamine eliminated this effect. These results indicate that living in a complex environment facilitates conditional freezing to an auditory CS, and that this effect is abolished by pretreatment with amphetamine.Housing in a relatively complex environment ("environmental enrichment") is known to alter the structure of dendrites (i.e., induce structural plasticity) in a variety of brain regions, and to also influence subsequent learning and memory. The first evidence for structural changes in the brain as a result of living in a complex environment was provided by Rosenzweig and colleagues in the 1960s, who reported that animals living in a complex environment showed increased cortical weight compared with animals in standard laboratory cages (Rosenzweig et al. 1962). Since that time, there have been many studies documenting a number of brain changes in rats living in a complex environment, including increases in cerebral volume, dendritic spine density and number, long-term potentiation (LTP), resistance to neural insult, and synaptic connectivity Greenough et al. 1985Greenough et al. , 1986Green and Greenough 1986; Kolb and Gibb 1991). Although these changes have been found in the cerebral cortex and other brain regions, the focus in many of these studies has been on the hippocampus. In addition to modifying hippocampal morphology, complex housing also enhances performance on a number of hippocampal-dependent learning tasks. The most welldocumented augmentation of learning after complex housing is in spatial tasks such as the Morris water maze and Hebb-Williams maze (Pham et al. 1999;Kobayashi et al. 2002). However, there is also evidence that environmental enrichment enhances Pavlovian fear conditioning in mice (Rampon et al. 2000;Duffy et al. 2001;Tang et al. 2001).Although these examples of experience-dependent plasticity are clearly advantageous, this is not true of all forms of experience-dependent plasticity. Repeated treatment with psychostimulant drugs, for example, also leads to an increase in dendritic branching and spine density in a number of brain regions, which is thought to be related to the development of behavioral sensitization (Robinson and Kolb 1997, 1999Robinson et al. 2001; Li et al. 2004). However, treatment with amphetamine or cocaine has also been shown to occlude the ability of subsequent exposure to a complex environment to alter dendritic structure (Kolb et al....

Lifelong environmental enrichment in rats: impact on emotional behavior, spatial memory vividness, and cholinergic neurons over the lifespan

“…In all age groups, enrichment attenuated contextual freezing. Even if this result is inconsistent with previous studies showing that enrichment tended to increase contextual fear (Briand et al 2005;Duffy et al 2001;Tang et al 2001), we previously showed (Barbelivien et al 2006) that if, in adult rats, enrichment increased fear to a background context (i.e., when a tone perfectly predicts footshock occurrence), it concomitantly decreased fear to a foreground context (i.e., no predictive tone), as found in the current study at all ages. Therefore, the lower freezing scores that we observed in enriched rats may reflect a genuine decrease in fear rather than a deficit in contextual conditioning.…”

Dissociation between long-lasting behavioral sensitization to amphetamine and impulsive choice in rats performing a delay-discounting task

“…Furthermore, our results suggest that the neuroadaptations that resulted from repeated AMPH exposure, which are known to be associated with sensitization (Robinson and Berridge 2000), do not cause enduring deficits in the aspects of cognition that the delay-discounting task requires. It is not clear from the current study if the observed dissociation is specific to the dosing procedure used, but it is notable that previous studies using similar AMPH treatment schedules have reported a reduction in subsequent structural plasticity and forms of new learning (Kolb et al 2003;Briand et al 2005), as well as impairments in object recognition memory (Bisagno et al 2003;Belcher et al 2006).…”

Memory and psychostimulants: modulation of Pavlovian fear conditioning by amphetamine in C57BL/6 mice

“…It has been reported that low-dose amphetamine (10 mg, p.o., damphetamine, approximately 0.12 mg/kg for an 80 kg person) given during speech therapy, leads to improved recovery from aphasia (Walker-Batson et al 2001). In order to examine amphetamine's effects on experience-dependent plasticity in rats, researchers examined fear conditioning in rats housed in a complex environment for 3 months (Briand et al 2005). While rats showed enhanced learning after living in the complex environment, rats treated with damphetamine (4.0 mg/kg) for 21 days, then housed in the enriched environment for 3 months, did not show the same enhancement.…”