Social and physical environment alter cocaine conditioned place preference and dopaminergic markers in adolescent male rats - PubMed (original) (raw)

Social and physical environment alter cocaine conditioned place preference and dopaminergic markers in adolescent male rats

E Zakharova et al. Neuroscience. 2009.

Abstract

This study was done to determine whether social and environmental factors alter cocaine reward and proteins implicated in mediating drug reward in rats during early adolescence. On postnatal day (PND) 23, rats were housed under conditions where both social (number of rats per cage) and environmental (availability of toys) factors were manipulated. Socially isolated rats were housed alone impoverished with no toys (II) or enriched with toys (IE). Social rats were housed two rats/cage with no toys (SI2) or with toys (SE2), or three/cage with (SE3) or without (SI3) toys. On PND 43, cocaine conditioned place preference (CPP) sessions began with the post-test done on PND 47. Cocaine CPP was established in response to 5 or 10 mg/kg cocaine in II rats, and CPP was decreased with the addition of cage mates or toys. No CPP was seen to any dose in SI3 or SE3 rats. Enriched housing (SE3) increased dopamine transporter (DAT) protein in the nucleus accumbens compared to II. There also were differential effects of cocaine on tyrosine hydroxylase and DAT depending on housing, with both increased by cocaine in II but not SE3 rats. DARPP-32 was unchanged by housing or cocaine, while phospho-Thr(34)-DARPP-32 was increased by cocaine treatment across conditions. Thus, both social and environmental enrichment decrease cocaine CPP during adolescence and different housing alters proteins that regulate dopaminergic neurotransmission in a manner that may account for the observed differences in cocaine-induced reward.

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Figures

Fig. 1

Fig. 1

Effects of 3, 5 and 10 mg/kg cocaine on conditioned place preference in groups of rats housed under different social and environmental conditions. SAL refers to groups trained with saline on both sides of the chamber. Data are presented as mean ± SEM preference values (time spent in cocaine-paired chamber minus time spent in saline-pared chamber during posttest expressed in seconds). CPP decreased as either social or environmental enrichment (rats and/or toys) was added to the cages (compare A, B, C). Both 5 and 10 mg/kg cocaine led to significant preferences in the II rats, whereas only 5 mg/kg cocaine produced a significant preference in the IE and SI2 rats. The SE2, SI3, and SE3 rats did not exhibit a significant preference in response to any of the doses tested. *significantly different from 0 (p<0.05).

Fig. 2

Fig. 2

Representative immunoblots of nucleus accumbens tissue from II and SE3 rats following vehicle (veh) or cocaine (coc) administration. Bands represent pTH, total TH, DAT, pDARPP-32 (Thr. 34), DARPP-32, and tubulin (from top to bottom).

Fig. 3

Fig. 3

TH, as measured by Western blot in the NA of rats housed in either II or SE3 conditions. (A) Total TH:tubulin is increased following 3 daily injections of cocaine in the II rats, but is unchanged in the SE3 rats. (B) In rats housed in the II condition, cocaine led to a significant increase in phosphorylated TH (pTH) in the NA. There was no effect of cocaine on pTH in the SE3 rats. Data shown are mean ± SEM; n=7–9/group; *P < 0.05 compared to II vehicle (VEH) treated rats.

Fig. 4

Fig. 4

DAT protein, measured by Western blot, in the NA of rats housed in either II or SE3 conditions. DAT is increased significantly in response to housing in the enriched environment (SE3) compared to the isolated environment (II). In addition, 3 daily injections of cocaine significantly increased DAT only in the rats housed in an impoverished condition. There was no effect of cocaine on DAT protein in the SE3 rats. Data shown are mean ± SEM; n=7–9/group; *P < 0.05 compared to vehicle (VEH).

Fig. 5

Fig. 5

DARPP-32, as measured by Western blot in the NA of rats housed in either II or SE3 conditions. (A) Total DARPP-32:tubulin is not significantly altered by either housing condition or by 3 daily injections of cocaine in either the II rats or the SE3 rats. (B) p-Thr34-DARPP-32 is increased across housing conditions in response to cocaine administration such that overall the cocaine-treated rats had higher levels of p-Thr34-DARPP-32 regardless of housing condition. Data shown are mean ± SEM; n=7–9/group.

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