Effects of adolescent methamphetamine and nicotine exposure on behavioral performance and MAP-2 immunoreactivity in the nucleus accumbens of adolescent mice

Abstract

The neurotoxic effects of methamphetamine (MA) exposure in the developing and adult brain can lead to behavioral alterations and cognitive deficits in adults. Previous increases in the rates of adolescent MA use necessitate that we understand the behavioral and cognitive effects of MA exposure during adolescence on the adolescent brain. Adolescents using MA exhibit high rates of nicotine (NIC) use, but the effects of concurrent MA and NIC in the adolescent brain have not been examined, and it is unknown if NIC mediates any of the effects of MA in the adolescent. In this study, the long-term effects of a neurotoxic dose of MA with or without NIC exposure during early adolescence (postnatal day 30-31) were examined later in adolescence (postnatal day 41-50) in male C57BL/6J mice. Effects on behavioral performance in the open field, Porsolt forced swim test, and conditioned place preference test, and cognitive performance in the novel object recognition test and Morris water maze were assessed. Additionally, the effects of MA and/or NIC on levels of microtubule associated-2 (MAP-2) protein in the nucleus accumbens and plasma corticosterone were examined. MA and NIC exposure during early adolescence separately decreased anxiety-like behavior in the open field test, which was not seen following co-administration of MA/NIC. There was no significant effect of early adolescent MA and/or NIC exposure on the intensity of MAP-2 immunoreactivity in the nucleus accumbens or on plasma corticosterone levels. These results show that early adolescent MA and NIC exposure separately decrease anxiety-like behavior in the open field, and that concurrent MA and NIC exposure does not induce the same behavioral change as either drug alone.

The effects of enriched environment on the behavioral and corticosterone response to methamphetamine in adolescent and adult mice

“…MA‐exposed adult mice had a higher percent of time immobile compared to saline‐exposed adult mice. The lack of a long‐term effect of MA on behavioral despair in adolescent mice replicates previous research (Buck et al, ), although it is in contrast to other studies showing adolescent MA exposure increases behavioral despair 16 days following exposure (Joca et al, ). Differences in the timing of Porsolt forced swim testing during adolescence may account for differences in these results.…”

“…The lack of a long‐term effect of adolescent MA exposure on locomotor activity and anxiety‐like behavior in the open field test replicates previous research in adolescent mice (Joca et al, ). However, other research shows decreased anxiety‐like behavior in adolescent mice on PND 41, 10 days following MA exposure (Buck et al, ). In our study, open field testing took place on PND 47, and thus differences in the age when open field testing takes place may account for differences in the results on anxiety‐like behavior.…”

“…injections (0.1 ml) of either saline or 7.5 mg/kg MA were administered four times daily at 2‐hr intervals on PND 30 and 31 for the adolescent mice and on PND 96 and 97 for the adult mice (saline treatment: n = 8 adolescent IE mice, n = 10 adolescent EE mice, n = 9 adult IE mice, n = 10 adult EE mice; MA treatment: n = 9 adolescent IE mice, n = 9 adolescent EE mice, n = 10 adult IE mice, n = 7 adult EE mice). This injection schedule and paradigm was chosen to replicate previous research examining the long‐term effects of adolescent MA exposure in mice (Buck et al, ; Good & Radcliffe, ; Joca et al, ). Treatments were counterbalanced within EE housing cages.…”

“…Studies using animal models have examined the effects of adolescent MA exposure; however, this literature is relatively sparse compared to that on the effects of adult MA exposure. These studies show that MA exposure during adolescence in mice causes long‐term increases in behavioral despair in the Porsolt forced swim test (Joca, Zuloaga, Raber, & Siegel, ) and decreases in anxiety‐like behavior (Buck, Morris, Weber, Raber, & Siegel, ). In contrast, MA exposure during adolescence increases anxiety‐like behavior later in adulthood in rats (Loxton & Canales, ).…”

“…Acute MA exposure immediately increases corticosterone levels in neonatal (Acevedo, Pfankuch, van Meer, & Raber, ; Grace et al, ; Williams et al, ; Zuloaga, Siegel, Acevedo, Agam, & Raber, ) and adult rodents (Braun et al, ; Herring et al, ; Zuloaga, Johnson, Agam, & Raber, ), but not in adolescent rodents (Rud, Do, & Siegel, ). MA causes long‐term increases in corticosterone levels in adult mice (Grace et al, ), but does not cause these long‐term changes in corticosterone levels in adolescent mice (Buck et al, ).…”