The effects of infusions of CART 55-102 into the basolateral amygdala on amphetamine-induced conditioned place preference in rats

Abstract

Rationale: The affective aspects of D: -amphetamine (AMPH) may be mediated, in part, by cocaine- and amphetamine-regulated transcript (CART) peptides in the basolateral amygdala (BLA). The formation of context-drug associations produces either conditioned place preference (CPP) or conditioned place aversion (CPA).

Objectives: The aim of the present study was to determine whether intra-BLA infusions of CART 55-102 are either rewarding or aversive and modulate AMPH reward.

Materials and methods: Rats were implanted with bilateral cannulae in the BLA, were subjected to place conditioning, and were tested for CPP or CPA. Rats were conditioned with either intra-BLA infusions of artificial cerebral spinal fluid or one of three dose of CART 55-102 (1, 2, or 4 microg/side), intra-BLA infusions of a subrewarding dose of CART 55-102 (1 microg/side) plus injections of a subrewarding dose of AMPH (0.1 mg/kg, i.p.), or intra-BLA infusions of an aversive dose of CART 55-102 (4 microg/side) plus injections of a rewarding dose of AMPH (1.0 mg/kg, i.p.).

Results: Intra-BLA infusions of 2 microg/side CART 55-102 produced CPP, 4 microg/side produced CPA, and 1 microg/side produced neither CPP nor CPA. Intra-BLA infusions of a subrewarding dose of CART 55-102 (1 microg/side) plus injections of a subrewarding dose of AMPH (0.1 mg/kg, i.p.) produced CPP. Intra-BLA infusions of an aversive dose of CART 55-102 (4 microg/side) plus injections of a rewarding dose of AMPH (1.0 mg/kg, i.p.) produced neither CPP nor CPA.

Conclusions: Both the affective properties of intra-BLA CART 55-102 and its ability to either facilitate or block AMPH reward are dose dependent.

Fig. 1

The effects of intra-BLA infusions of aCSF or CART (1, 2, 4 µg) on a time spent in each conditioning compartment during the place conditioning test and b locomotor activity on each of the conditioning days. Significant difference between time spent in the aCSF-paired and CART-paired compartment during the place conditioning test, **p< 0.01. Each bar in the graph represents the mean of six to nine rats; vertical lines represent SEM

Fig. 2

Effects of intra-BLA infusions either aCSF or a dose of CART 55–102 that does not produce CPP or CPA plus either saline or a dose of AMPH that does not produce CPP or CPA on a time spent in each conditioning compartment during the place conditioning test and b locomotor activity on each of the conditioning days. Significant difference between time spent in the aCSF- and saline-paired compartment and the CART 55–102- and AMPH-paired compartment during the place conditioning test, **p<0.01. Each bar in the graph represents the mean of seven to 12 rats; vertical lines represent SEM

Fig. 3

Effects of intra-BLA infusions of a dose of CART 55–102 that produces CPA plus systemic administration of a dose of AMPH that produces CPP on a time spent in each conditioning compartment during the place conditioning test and b locomotor activity on each of the conditioning days. Significant difference in the number of infrared beam breaks between animals treated with aCSF plus saline compared to those treated with CART 55–102 (4 µg/side) plus AMPH (1.0 mg/kg, i.p.), ***p<0.001. Significant difference in the number of beam breaks on conditioning day 5 compared to conditioning day 1 for animals treated with CART 55–102 (4 µg/side) plus AMPH (1.0 mg/kg, i.p.), *p<0.05. Each bar in the graph represents the mean of nine to 13 rats; vertical lines represent SEM

Fig. 4

The effect of injections of either saline or AMPH (1.0 mg/kg) on a time spent in each conditioning compartment during the place conditioning test and b locomotor activity on each of the conditioning days for rats that previously received intra-BLA infusions of a dose of CART 55–102 that produces CPA plus systemic administration of a dose of AMPH that produces CPP. Significant difference between the time spent in the saline-paired and the AMPH-paired compartment during the place conditioning test, ***p<0.001. Significant difference in the number of infrared beam breaks between animals reconditioned with a rewarding dose of AMPH (1.0 mg/kg, i.p.) compared to animals reconditioned with saline, ***p<0.001. Significant difference in the number of infrared beam breaks on conditioning day 13 compared to conditioning day 9 for animals reconditioned with AMPH (1.0 mg/kg, i.p.), **p<0.01. Each bar in the graph represents the mean of nine to 13 rats; vertical lines represent SEM

Fig. 5

Histological verification of the infusion sites. Photomicrographs of Nissl-stained coronal sections showing the representative placements for the bilateral BLA infusion sites (indicated by the arrows). Open circles mark the most ventral sites of the infusions for each targeted brain structure. Infusion sites in the BLA are illustrated in the column to the left; caudate–putamen sites are illustrated in the column to the right. Numbers to the left of the panels indicate millimeters from the bregma. Stereotaxic maps were reproduced, with permission from Elsevier Science, from a brain atlas (Paxinos and Watson 2007)