title: Transgenerational effects of paternal heroin addiction on anxiety and aggression behavior in male offspring.
abstract: BACKGROUND
  Heroin addiction is a growing concern, affecting the socioeconomic development of many countries. Little is known about transgenerational effects on phenotype changes due to heroin addiction. This study aims to investigate changes in level of anxiety and aggression up to four different generations of adult male rats due to paternal exposure to heroin.
  
  
  METHODS
  Male Sprague-Dawley rats were exposed with heroin intraperitoneally (i.p.) twice-daily for 14 days with increasing dosage regimen (F0-heroin). Male Sprague-Dawley rats (6-weeks-old) were divided into: (1) heroin exposed group (F0-heroin) and (2) control group treated with saline solution (F0-control). The dosage regime started with the lowest dose of 3 mg/kg per day of heroin followed by 1.5 mg/kg increments per day to a final dose of 13.5 mg/kg per day. Offspring were weaned on postnatal day 21. The adult male offspring from each generation were then mated with female-naïve rats after 2 weeks of heroin absence. Open field test and elevated plus maze test were used to study the anxiety level, whereas resident intruder test was used to evaluate aggression level in the addicted male rats and their offspring.
  
  
  RESULTS
  Heroin exposure in male rats had resulted in smaller sizes of the litters compared to the control. We observed a higher anxiety level in the F1 and F2 progenies sired by the heroin exposed rats (F0) as compared to the control rats. Paternal heroin exposure also caused significantly more aggressive offspring in F1 compared to the control. The same pattern was also observed in the F2.
  
  
  CONCLUSIONS
  Our results demonstrated that the progenies of F1 and F2 sustained higher levels of anxiety and aggression which are due to paternal heroin exposure.
authors: Integrative Pharmacogenomics Institute (iPROMISE), Level 7, FF3, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia.|Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia.
authors: Mohd Zaki
authors: MZ
authors: Farah Naquiah
authors: Integrative Pharmacogenomics Institute (iPROMISE), Level 7, FF3, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia. ritchjj@yahoo.fr.|Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia. ritchjj@yahoo.fr.
authors: Richard Johari
authors: RJ
authors: James
authors: Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia.
authors: Suraya
authors: S
authors: Suratman
authors: Integrative Pharmacogenomics Institute (iPROMISE), Level 7, FF3, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia.
authors: Lian Shien
authors: LS
authors: Lee
authors: Comparative Medicine and Technology Unit, Institute Bioscience, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
authors: Mohd Izhar
authors: MI
authors: Mohd Hafidz
authors: Integrative Pharmacogenomics Institute (iPROMISE), Level 7, FF3, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia.|Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia.
authors: Mohd Zaki
authors: MZ
authors: Salleh
authors: Integrative Pharmacogenomics Institute (iPROMISE), Level 7, FF3, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia. tehlaykek2016@gmail.com.|Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia. tehlaykek2016@gmail.com.
authors: Lay Kek
authors: LK
authors: Teh
mesh_terms: D000374:Aggression / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000523:psychology*; D001008:Anxiety Disorders / Q000235:genetics / Q000523:psychology; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006556:Heroin Dependence / Q000235:genetics* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018812:Paternal Exposure / Q000009:adverse effects; D000072740:Paternal Inheritance / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Aggression; Anxiety; Male offspring; Paternal heroin addiction; Transgenerational effects