Age-dependent differences in the strength and persistence of psychostimulant-induced conditioned activity in rats

McDougall, Sanders A.; Pipkin, Joseph A.; Der-Ghazarian, Taleen; Cortez, Anthony M.; Gutierrez, Arnold; Lee, Ryan J.; Carbajal, Sandra; Mohd-Yusof, Alena

doi:10.1097/fbp.0000000000000085

Cited by 7 publications

(6 citation statements)

References 54 publications

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“…Regardless of habituation day, adult rats exhibited more locomotor activity than preweanling rats, with adolescent rats being intermediate between and significantly different from the younger and older age groups. The finding that preweanling rats locomoted less than adults has been observed before in both habituated and nonhabituated animals (McDougall et al 2007, 2014a; but see Campbell et al 1969). Less clear is the relationship between adolescents and adults, because adult rats and mice were found to exhibit more (Adriani and Laviola 2000; Koek et al 2012; McDougall et al 2014a), less (Lanier and Isaacson 1977; Spear and Brake 1983), or similar levels of basal locomotor activity when compared to adolescent rodents (White and Holtzman 2005; Zombeck et al 2010).…”

Section: Discussionsupporting

confidence: 69%

Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

et al. 2015

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Rationale Responsiveness to acute psychostimulant administration varies across ontogeny. Objective The purpose of the present study was to determine if age-dependent changes in D2High receptors may be responsible for the ontogeny of cocaine sensitivity in preweanling, adolescent, and adult rats. Methods [3H]-Domperidone/dopamine competition assays were used to determine ontogenetic changes in the proportion of D2High receptors in male and female preweanling [postnatal day (PD) 5, 10, 15, and 20], adolescent (PD 40), and adult rats (PD 80). In the behavioral experiment, responsiveness to cocaine (2.5, 5, 10, or 20 mg/kg) was assessed on PD 20, PD 40, and PD 80 for 60 min. Male and female rats were habituated to the apparatus on the two days prior to testing. Distance traveled data were presented both untransformed and as percent of saline controls. Results Male and female preweanling rats (PD 5–PD 20) had a significantly greater percentage of dorsal striatal D2High receptors than adolescent or adult rats. Likewise, preweanling rats (PD 20) were more sensitive to the behavioral effects of cocaine than the two older age groups. Adolescent and adult rats responded in a generally similar manner, however analysis of the untransformed locomotor activity data suggested that adolescent rats were hyporesponsive to 2.5 and 20 mg/kg cocaine when compared to adults. Conclusions Data from the present study are consistent with the hypothesis that ontogenetic changes in D2High receptors are responsible for age-dependent differences in psychostimulant sensitivity.

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Section: Discussionsupporting

confidence: 69%

Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

et al. 2015

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“…In the animals treated with IN-DA before VEH, these behaviors did not decrease in comparison with VEH, suggesting DA conditioned behavioral effects as a likely cause, i.e., the normal behavioral response to VEH could have been masked or modified as a result of Pavlovian conditioning of the unconditioned response to the preceding IN-DA. Such an interpretation is consistent with a large literature describing Pavlovian conditioned behavioral responses and sensitization to psychoactive drugs, such as cocaine and amphetamine (Carey et al, 2014 ), and particularly with the results of McDougall et al ( 2014 ), who found one-trial induced cocaine conditioned activity, which persisted for at least 21 days in rats. This interpretation is also consistent with the evidence above for a Pavlovian conditioned DA response to VEH when VEH was preceded by IN-DA.…”

Section: Discussionsupporting

confidence: 91%

“…Signaling by extracellular signal-regulated kinase (ERK) has also been shown to play a role in Pavlovian psychostimulant conditioning (Lu et al, 2006 ). One-trial induced Pavlovian conditioned behavioral response to cocaine has been shown to persist for at least 21 days in rats (McDougall et al, 2014 ). Such results lend credence to an interpretation of our results in terms of Pavlovian drug conditioning to IN-DA.…”

Section: Discussionmentioning

confidence: 99%

“…The application of psychostimulant drugs, such as amphetamine and cocaine, is well known to result in Pavlovian-like conditioned behavioral activation and DA sensitization in rodents (Carey and Damianopoulos, 1992 ; Carey and Gui, 1998 ; Carey et al, 2005 ). Even a single drug application can result in long-lasting Pavlovian conditioning (McDougall et al, 2014 ). In PD patients, conditioned DA release in the striatum of PD patients to placebo treatment was reported using competition for [11C] raclopride binding as measured by positron emission tomography (de la Fuente-Fernández et al, 2001 ; Lidstone et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

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Intranasal Dopamine Reduces In Vivo [123I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response

Silva

Mattern

Decheva

et al. 2016

Front. Behav. Neurosci.

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Purpose: Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [123I]FP-CIT to the DAT should be decreased due to competition at the receptor.Methods: Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [123I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand.Results: (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs.Conclusions: The results: (a) demonstrate a direct central action of intranasally applied DA on the DAT in the dorsal striatum, indicating enhanced DA availability; and (b) provide first evidence of a Pavlovian conditioned DA response at the DAT. The latter results have relevance to understanding neurochemical mechanisms that underlie placebo action in the treatment of Parkinsonian patients.

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“…One possibility is that the inability of ketamine to induce conditioned activity is unique to early ontogeny. Indeed, preweanling rats (PD 10–PD 21) do not show cocaine-induced conditioned activity even after 10 daily environment-drug pairings (Zavala et al 2000; see also Wood et al 1998; McDougall et al 1999; 2014). The reason for this age-dependent effect is unknown, but Spear and colleagues have shown that young rats perceive and process CSs differently than adults (for reviews, see Spear et al 1988; Spear and McKenzie 1994).…”

Section: Discussionmentioning

confidence: 99%

Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose

et al. 2017

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Rationale Ketamine is used by preadolescent and adolescent humans for licit and illicit purposes. Objective The goal of the present study was to determine the effects of acute and repeated ketamine treatment on the unconditioned behaviors and conditioned locomotor activity of preadolescent and adolescent rats. Methods To assess unconditioned behaviors, female and male rats were injected with ketamine (5–40 mg/kg) and distance traveled was measured on PD 21–25 or PD 41–45. To assess conditioned activity, male and female rats were injected with saline or ketamine in either a novel test chamber or the home cage on PD 21–24 or PD 41–44. One day later, rats were injected with saline and conditioned activity was assessed. Results Ketamine produced a dose-dependent increase in the locomotor activity of preadolescent and adolescent rats. Preadolescent rats did not exhibit sex differences, but ketamine-induced locomotor activity was substantially stronger in adolescent females than males. Repeated ketamine treatment neither caused a day-dependent increase in locomotor activity nor produced conditioned activity in preadolescent or adolescent rats. Conclusions The activity-enhancing effects of ketamine are consistent with the actions of an indirect dopamine agonist, while the inability of ketamine to induce conditioned activity is unlike what is observed after repeated cocaine or amphetamine treatment. This dichotomy could be due to ketamine’s ability to both enhance DA neurotransmission and antagonize NMDA receptors. Additional research will be necessary to parse out the relative contributions of DA and NMDA system functioning when assessing the behavioral effects of ketamine during early ontogeny.

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Age-dependent differences in the strength and persistence of psychostimulant-induced conditioned activity in rats

Cited by 7 publications

References 54 publications

Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

Intranasal Dopamine Reduces In Vivo [123I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response

Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose

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